Breast Cancer Treatment Trials

 Click on any of the Breast Cancer Treatment Trials below to learn more:

(1) CALGB-40502: Phase III Randomized Study of Paclitaxel Versus Paclitaxel Albumin-Stabilized Nanoparticle Formulation Versus Ixabepilone With or Without Bevacizumab in Patients With Stage IIIC or IV Breast Cancer (The ixabepilone arm has been closed as of 8/15/11)

Primary Objectives: To compare the progression-free survival of patients with stage IIIC or IV breast cancer treated with paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel) versus ixabepilone (This arm has been closed as of 7/18/11) versus paclitaxel with or without bevacizumab.

Entry Criteria 

Disease Characteristics:

• Histologically confirmed invasive breast cancer
  • Stage IIIC or IV (locally recurrent or metastatic) disease not amenable to local therapy
• Measurable disease (target lesions), defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 2.0 cm with conventional techniques or as ≥ 1 cm with spiral CT scan
• No non-measurable lesions, including any of the following:
  • Ascites
  • Pleural/pericardial effusion
  • Inflammatory breast disease
  • Lymphangitis cutis/pulmonitis
  • Bone lesions
  • Leptomeningeal disease
  • Cystic lesions
  • Abdominal masses not confirmed and followed by imaging techniques
• HER2/neu status must be known
  • HER2-positive disease allowed provided patient received prior trastuzumab (Herceptin®) or lapatinib (documentation of progression on HER2-directed therapy is not required)
• No progressing or untreated CNS metastases or leptomeningeal disease
  • History of resected brain metastases with stable MRI scans for 3 months, including within the past 4 weeks allowed
  • History of gamma-knife radiosurgery or whole-brain radiation with stable MRI scans for 3 months, including within the past 4 weeks allowed
• Hormone receptor status must be known
  • Estrogen receptor (ER)- and progesterone receptor (PgR)-positive if ≥ 1% cells are positive

Prior/Concurrent Therapy:

• See Disease Characteristics
• No prior chemotherapy regimen for metastatic disease
• Adjuvant or neoadjuvant taxane allowed provided interval between completion of adjuvant therapy and disease recurrence is ≥ 12 months
• At least 2 weeks since prior radiotherapy
• At least 28 days since prior major surgical procedure or open biopsy and fully recovered
  • There are no restrictions on core biopsies, placement of a vascular access device, or other minor procedures prior to registration.
• At least 7 days since prior hormonal therapy
  • Any number of prior hormonal therapies allowed
• Prior trastuzumab or lapatinib ditosylate for HER2-overexpressing tumors allowed
• Prior bevacizumab allowed
• Prior and concurrent bisphosphonate treatment allowed
• No concurrent major surgical procedure
• No concurrent palliative radiotherapy
• No concurrent aprepitant
• No concurrent pegfilgrastim
• No other concurrent chemotherapy or anticancer hormone therapy
• Concurrent full-dose anticoagulants allowed but patient must be on a stable dose of warfarin or low molecular weight heparin
  • Anti-platelet therapy or on daily prophylactic-dose aspirin allowed
  • Stable doses of anticoagulation for atrial fibrillation allowed

Patient Characteristics:

• Menopausal status not specified
• ECOG (Zubrod) performance status 0-1
• Life expectancy ≥ 12 weeks
• Granulocytes ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Creatinine ≤ 2.0 mg/dL
• Bilirubin < 1.5 mg/dL (unless due to Gilbert's syndrome)
• AST and ALT ≤ 2.5 times upper limit of normal
• Urine protein ≤ 1+ OR urine protein:creatinine ratio < 1
  • Patients with proteinuria ≥ 2+ at baseline must undergo a 24-hour urine collection that demonstrates < 1 g of protein/24 hr or UPC ratio ≤ 1
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• History of seizures allowed if well controlled with standard medication
• No history of hypersensitivity to paclitaxel or Cremophor® EL CTCAE grade ≥ 3
• No other active malignancy except nonmelanoma skin cancer (patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to have less than 30% risk of relapse)
• No history of abdominal fistula or intra-abdominal abscess within 6 months prior to study registration
• No history of gastrointestinal (GI) perforation within the past 12 months
• No history of significant bleeding episodes (e.g., hemoptysis, upper or lower GI bleeding) within the past 6 months
• No history of stroke or transient ischemic attack within the past 6 months
• No history of clinically significant cardiovascular disease including any of the following:
  • Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg and/or diastolic BP > 90 mm Hg on antihypertensive medications
  • Prior history of hypersensitivity or hypertensive encephalopathy
  • History of myocardial infarction or unstable angina within past 6 months
  • NYHA congestive heart failure class II-IV
  • Symptomatic peripheral vascular disease
  • Significant vascular disease (e.g., aortic aneurysm or aortic dissection) or arterial thrombotic events
• No serious, non-healing wound, ulcer, or bone fracture
• No significant traumatic injury in the past 28 days
• No peripheral neuropathy ≥ grade

Outline

This is a multicenter study. Patients are stratified according to taxane as adjuvant therapy (yes or no), estrogen receptor (ER) or progesterone receptor (PgR) status (ER-positive or PgR-positive vs both ER-negative and PgR-negative), physician's decision to use bevacizumab (yes vs no). Patients are randomized to 1 of 3 treatment arms.

• Arm I (weekly paclitaxel): Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15. Patients may also receive bevacizumab IV over 30-90 minutes on days 1 and 15.
• Arm II (weekly paclitaxel albumin-stabilized nanoparticle formulation [nab-paclitaxel]): Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Patients may also receive bevacizumab as in arm I.
• Arm III (weekly ixabepilone): Patients receive ixabepilone IV over 60 minutes on days 1, 8, and 15. Patients may also receive bevacizumab as in arm I. (This arm has been closed as of 7/18/11)

In all arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients complete questionnaires about peripheral neuropathy at baseline and before each course of therapy. They also complete questionnaires about sociodemographics, non-cancer comorbidities, social support, physical activity, and post-trial therapy at baseline and periodically thereafter.

Blood samples may be collected at baseline and periodically during study for correlative studies. Tumor tissue samples from diagnosis may be also collected.

After completion of study therapy, patients are followed every 6 months for 2 years and then annually for up to 3 years. 

If you are interested in this breast cancer research study, please contact:

Venita Alston Crawford, RN, BSN

Clinical Research Nurse Coordinator

crawfv@holycrosshealth.org

301-754-8556

Principal Investigator:
Cheryl Aylesworth, MD, Medical Oncologist

(2) CALGB-40601: Phase III Randomized Study of Neoadjuvant Paclitaxel in Combination With Trastuzumab (Herceptin®) With or Without Lapatinib Ditosylate in Patients With HER2-Positive Resectable Stage II or III Breast Cancer

Primary Objectives: To compare the pathologic complete response (pCR) in the breast of patients with HER2-positive resectable stage II or III breast cancer treated with neoadjuvant paclitaxel and trastuzumab (Herceptin®) with or without lapatinib ditosylate.

Entry Criteria 

Disease Characteristics:

• Pathologically confirmed invasive breast cancer by core needle or incisional biopsy
  • Clinical stage II or III disease
  • Resectable disease
• HER2-positive tumor, defined as 3+ overexpression by IHC or gene amplification by FISH with a ratio of ≥ 2 on invasive tumor
• Measurable disease, defined as target lesion in the breast ≥ 1 cm by physical examination or radiographic measurement
  • No axillary disease only
• Multicentric or bilateral disease allowed provided the target lesion meets eligibility criteria
• Planning to undergo surgical resection after neoadjuvant therapy
• No inflammatory breast cancer
• No metastatic disease
• Concurrent enrollment in CALGB-150702 required
• Hormone receptor status known

Prior/Concurrent Therapy:

• See Disease Characteristics
• No prior chemotherapy, hormonal therapy, biologic therapy, or radiotherapy for the treatment of breast cancer
• No other concurrent chemotherapy or hormonal therapy, except for the following:
  • Steroids for adrenal failure
  • Hormones for non-disease-related conditions (e.g., insulin for diabetes)
  • Intermittent use of dexamethasone as an antiemetic
• No concurrent pegfilgrastim

Patient Characteristics:

• Menopausal status not specified
• ECOG (Zubrod) performance status 0-1
• ANC ≥ 1,000/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective non-hormonal contraception during and for ≥ 2 months after completion of study treatment
• Cardiac ejection fraction ≥ 50% by echocardiogram or MUGA scan
• Willing to undergo pretreatment biopsies and submit archival tissue obtained at the time of surgery

Outline

This is a multicenter study. Patients are stratified according to pretreatment clinical stage (II vs III) and hormone receptor status (estrogen receptor [ER]- and/or progesterone receptor [PR]-positive vs ER- and PR-negative). Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes and paclitaxel IV over 1 hour once weekly and oral lapatinib ditosylate once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive trastuzumab and paclitaxel as in arm I.
• Arm III: Patients receive paclitaxel and lapatinib ditosylate as in arm I. (Discontinued as of 6-15-11)

Within 42 days after completion of neoadjuvant therapy, patients in both arms undergo definitive surgery (breast conservation or total mastectomy). Patients may then receive adjuvant therapy (e.g., radiotherapy, hormonal therapy, and/or additional chemotherapy and trastuzumab) at the discretion of the treating physician.

Tumor tissue samples are collected at baseline for correlative laboratory studies. Samples are analyzed for biomarkers (e.g., HER2, IGF1R, Ki67, apoptosis, PIK3CA, PTEN, Topo II, c-myc, EGFR, HER3, HER4, 2CF, Erk ½, AKT, and other biomarkers) by quantitative RT-PCR, IHC, TUNEL assay, FISH, gene expression array, and comparative genomic hybridization.

After completion of study treatment, patients are followed every 6 months for 2 years and then annually for up to 10 years. 

If you are interested in this breast cancer research study, please contact:

Venita Alston Crawford, RN, BSN

Clinical Research Nurse Coordinator

crawfv@holycrosshealth.org

301-754-8556

Principal Investigator:
Cheryl A. Aylesworth, M.D., Medical Oncologist

(3) CALGB-70305: Randomized Study of Education With or Without Exercise and Counseling in Preventing Lymphedema in Women With Stage I-III Breast Cancer Who Are Undergoing Axillary Lymph Node Dissection 

Primary Objectives: Determine the efficacy of a comprehensive program of tailored exercise, lymphedema prevention patient education, and counseling vs lymphedema prevention patient education only in reducing the incidence of lymphedema in women with stage I-III breast cancer who are undergoing axillary lymph node dissection.

Entry Criteria 

Disease Characteristics:

• Diagnosis of breast cancer
  • Newly diagnosed disease
  • Stage I-III disease
• No diagnosed lymphedema
• Must have arm measurements for axilla, elbow, and wrist that fall within the ranges for one of six sleeve sizes (i.e., all three measurments must be found in one column) available
• Scheduled to undergo axillary node dissection with ≥ 10 nodes removed
  • No sentinel axillary node dissection only
• Hormone receptor status not specified

Prior/Concurrent Therapy:

• See Disease Characteristics
• No prior double mastectomy, axillary node dissection, and/or radiotherapy involving both arms
  • Prior treatment (i.e., surgergy and/or radiotherapy) on the contralateral arm allowed provided it is documented appropriately
• May be enrolled on other treatment trials except surgery trials where one treatment arm involves full axillary node dissection
  • Patients enrolled on ACOSOG-Z1071 allowed
• Any type of radiotherapy to the breast or axilla allowed
• Neoadjuvant treatment for this cancer allowed

Patient Characteristics:

• Female
• Menopausal status not specified
• No documented cardiac conduction disturbances, unstable angina, dementia, or any other chronic disease that, in the opinion of the investigator, significantly increases mortality over the next 2 years
• May not be currently homebound or dependent upon a walker or wheelchair for mobility
• Able to participate in a mild exercise program
• No prior history of carcinoma in situ, lobular carcinoma in situ, ductal carcinoma in situ, or invasive breast cancer
  • Patients with a history of other invasive malignancies are eligible as long as they have completed treatment and are 5 years post-diagnosis
  • Patients with basal cell and squamous cell carcinoma of the skin are eligible

Outline

This is a randomized, controlled, multicenter study where the unit of randomization is the participating center. Participating centers are stratified according to the annual number of patients with stage I-III breast cancer who undergo axillary node dissection at the center (small vs moderate vs large number of patients) and are randomized to 1 of 2 arms. Patients are thus randomized to 1 of 2 intervention arms based on the identified participating center.

All patients complete questionnaires prior to surgery regarding lymphedema knowledge, health-related quality of life, fear of cancer recurrence, self-efficacy, body-image, self-report of range of motion, arm circumference, and demographics. Patients then undergo surgery, which must include axillary node dissection.

• Arm I: Six weeks after surgery, patients receive a brief initial post-operative care session describing lymphedema risk and prevention through oral instruction and written materials. Patients complete physical assessments and questionnaires at 6 weeks and at 6, 12, and 18 months. Patients are also contacted by telephone at 9 and 15 months.
• Arm II: Patients receive lymphedema education and complete physical assessments and questionnaires as in arm I. Patients also complete a personalized exercise regimen, receive a refrigerator magnet, and a 15-minute video that reinforces information and exercises.

If you are interested in this breast cancer research study, please contact:

Venita Alston Crawford, RN, BSN

Clinical Research Nurse Coordinator

crawfv@holycrosshealth.org

301-754-8556

Principal Investigator:
Cheryl A. Aylesworth, M.D., Medical Oncologist

(4) NCCTG-N0733: Phase II Randomized Study of Capecitabine and Lapatinib Ditosylate With Versus Without Cixutumumab in Patients With Previously Treated HER2-Positive Stage IIIB, IIIC, or IV Breast Cancer 

Primary Objectives: To compare the progression-free survival of patients with HER2-positive stage IIIB, IIIC, or IV breast cancer treated with lapatinib ditosylate and capecitabine with vs without cixutumumab. 

Entry Criteria 

Disease Characteristics:

• Histologically confirmed breast cancer, meeting one of the following criteria:
  • Locally advanced disease (i.e., stage IIIB or IIIC [T4 primary tumor] disease)
  • Metastatic disease
• Disease progressed after treatment with regimens that included trastuzumab (Herceptin®) in combination with an anthracycline and/or a taxane
  • Agents need not have been given concurrently, nor in the same regimen
  • Prior chemotherapy regimens in the neoadjuvant, adjuvant, or metastatic setting allowed
    • Unlimited prior chemotherapy is allowed
  • Prior treatment with trastuzumab required unless there is a contraindication for trastuzumab treatment
• HER2-positive disease, defined by any of the following:
  • Validated IHC assay score of 3+ (defined as uniform, intense staining of > 30% of invasive tumor cells)
  • Average HER2 gene copy number > 6
  • Gene amplified (HER2:D17Z1 ratio > 2.20)
• Measurable disease according to RECIST criteria
• No evidence of active brain metastases, including leptomeningeal involvement
  • CNS metastasis controlled* by prior surgery and/or radiotherapy is allowed

 [Note: *To be considered controlled, there must have been no symptoms for at least 2 months or no evidence of progression prior to study entry AND corticosteroid therapy must have been discontinued]

• Hormone receptor status not specified

Prior/Concurrent Therapy:

• See Disease Characteristics
• Prior hormonal therapy in the neoadjuvant, adjuvant, or metastatic setting allowed
• More than 6 weeks since prior major surgery, chemotherapy, or immunologic therapy
• More than 4 weeks since prior radiotherapy, except a single dose of palliative radiotherapy or radiotherapy to a non-target lesion
  • Prior radiotherapy to a target lesion is allowed only if there has been clear progression of the lesion since completion of radiotherapy
  • Recovered from prior radiotherapy
• No more than 2 prior chemotherapy regimens for metastatic disease
• No prior treatment with any therapy targeting IGF-I, IGF-II, or its receptors (either monoclonal antibody or tyrosine kinase inhibitor) including, but not limited to, any of the following:
  • Cixutumumab
  • CP-751871
  • AMG-479
  • INSM-18
  • MK-0646 (h7C10)
  • 19D12
  • R1507
  • OSI-906
  • BMS-536924
  • PPP
  • NVP-AEW541
• No other prior therapy targeting HER1 (EGFR) and/or HER2 (either monoclonal antibody or tyrosine kinase inhibitor) including, but not limited to, any of the following:
  • Lapatinib ditosylate
  • Gefitinib
  • Erlotinib hydrochloride
  • Cetuximab
  • Panitumumab
• No concurrent agents that would contraindicate study treatment, including any of the following:
  • CYP3A4 inhibitors and inducers, including grapefruit and grapefruit juice
  • Warfarin, cimetidine, allopurinol, sorivudine or brivudine, ketoconazole, itraconazole, ritonavir, amprenavir, or indinavir
• No concurrent treatment in another clinical study in which investigational procedures are performed or investigational therapies are administered
• No other concurrent chemotherapeutic agents, biologic agents, or radiotherapy
• No other concurrent trastuzumab

Patient Characteristics:

• Menopausal status not specified
• ECOG performance status 0-2
• Life expectancy > 3 months
• WBC ≥ 3,000/mm³
• ANC ≥ 1,500/mm³
• Platelet count ≥ 75,000/mm³
• Hemoglobin > 9.0 g/dL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN (5 times ULN if elevations are due to liver metastases)
• Serum creatinine ≤ 1.5 times ULN
• Creatinine clearance ≥ 30 mL/min
• Fasting glucose < 120 mg/dL
  • Diabetes allowed provided blood glucose level meets the above criterion
• INR ≤ 1.5 times ULN
• LVEF ≥ 50% by MUGA or ECHO
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Willing to provide tissue and blood samples for research purposes
• Able to complete questionnaires by self or with assistance
• No other stage III or IV invasive cancer within the past 5 years
• No other malignancy requiring active treatment, except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • History of prior malignancy allowed provided patient is not receiving other specific treatment for their malignancy
• No current, active hepatic or biliary disease, except Gilbert syndrome's or asymptomatic gallstones
• No New York Heart Association class III or IV cardiovascular disease
• No concurrent uncontrolled illness including, but not limited to, any of the following:
  • Poorly controlled diabetes
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situation that would preclude compliance with study requirements
• No co-morbid systemic illness or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of the safety of the prescribed study regimens
• Not immunocompromised (other than that related to the use of corticosteroids), including known HIV-positivity with an AIDS-defining illness
  • HIV-positive patients with a CD4 count within normal range and who have no history of an AIDS-defining illness are eligible

Outline

This is a multicenter study. Patients are stratified according to hormone receptor status (estrogen receptor- or progesterone receptor-positive vs other) and number of prior chemotherapy regimens in the metastatic setting (2 or more vs 1 vs none). The first 10 patients enrolled on this study are assigned to cohort 1 (safety analysis). All other patients are assigned to cohort 2 (randomized treatment).

• Cohort 1 (safety analysis): Patients receive cixutumumab IV over 1-1½ hours on days 1, 8, and 15. Patients also receive oral capecitabine twice daily on days 1-14 and oral lapatinib ditosylate once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
• Cohort 2 (randomized treatment): Patients are randomized to 1 of 2 treatment arms.
  • Arm I: Patients receive oral capecitabine twice daily on days 1-14 and oral lapatinib ditosylate once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive capecitabine and lapatinib ditosylate as in arm I. Patients also receive cixutumumab IV over 1-1½ hours on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and on day 8 of courses 1 and 2 for biomarker laboratory studies. Serum and circulating tumor cell biomarkers are analyzed by immunohistochemistry or immunofluorescence for changes in protein expression (total and phosphorylated). Tumor tissue samples obtained at the time of original diagnosis are analyzed by immunohistochemistry for protein biomarkers.

Patients complete quality of life questionnaires periodically.

After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.

If you are interested in this breast cancer research study, please contact:

Venita Alston Crawford, RN, BSN

Clinical Research Nurse Coordinator

crawfv@holycrosshealth.org

301-754-8556

Principal Investigator:
Cheryl A. Aylesworth, M.D., Medical Oncologist

(5) NSABP-B-43: Phase III Randomized Study of Radiotherapy With Versus Without Trastuzumab (Herceptin®) in Women With HER2-Positive Ductal Carcinoma In Situ Who Underwent Lumpectomy

Primary Objectives: To determine the value of radiotherapy with vs without trastuzumab (Herceptin®) in preventing subsequent occurrence of ipsilateral breast cancer recurrence, ipsilateral skin cancer recurrence, or ipsilateral ductal carcinoma in situ (DCIS) in women with HER2-positive DCIS resected by lumpectomy.

Entry Criteria 

Disease Characteristics:

• Histologically confirmed ductal carcinoma in situ (DCIS)
  • Mixed DCIS and lobular carcinoma in situ (LCIS) allowed
• HER2 receptor-positive as determined by central testing
• Must have undergone resection by lumpectomy and meets the following criteria:
  • Margins of the resected specimen must be histologically free of DCIS (re-excision to obtain clear margins allowed)
  • No more than 120 days since the last surgery for excision of DCIS (lumpectomy or re-excision of lumpectomy margins)
• None of the following allowed:
  • Patients who require mastectomy
  • Invasive (including microinvasion staged as T1mic) breast cancer (DCIS “suspicious” for microinvasion, but not confirmed, allowed)
  • Nodal staging of pN1 (including pN1mi) (axillary staging not required)
  • DCIS present in more than one quadrant (multicentric)
  • Masses or clusters of calcification that are clinically or mammographically suspicious unless biopsied and proven to be benign
  • Contralateral breast cancer (including DCIS)
  • History of breast cancer, including DCIS (history of LCIS allowed)
• Hormone receptor status:
  • Estrogen receptor and/or progesterone receptor-positive or -negative
• Must submit tumor block for correlative studies

Prior/Concurrent Therapy:

• See Disease Characteristics
• No prior whole or partial breast irradiation
• No prior anthracycline chemotherapy for any malignancy
• No investigational agents within the past 30 days
• No other cancer therapy until the time of first cancer recurrence or second primary cancer

Patient Characteristics:

• Pre- or postmenopausal
• ECOG performance status 0-1
• Life expectancy ≥ 10 years (excluding diagnosis of DCIS)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective non-hormonal contraception during and for 6 months after completion of treatment with trastuzumab (Herceptin®)
• No psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements
• No cardiac disease that would preclude the use of study treatment drugs, including, but not limited to, any of the following:
  • Active cardiac disease
    • Angina pectoris that requires the use of anti-anginal medication
    • Ventricular arrhythmias except for benign premature ventricular contractions controlled by medication
    • Conduction abnormality requiring a pacemaker
    • Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
    • Clinically significant valvular disease
  • History of cardiac disease
    • Myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular function
    • Documented congestive heart failure
    • Documented cardiomyopathy
• No uncontrolled hypertension (i.e., systolic BP > 180 mm Hg and/or diastolic BP > 100 mm Hg) (hypertension that is well controlled on medication allowed)
• No other nonmalignant systemic disease that would preclude a patient from receiving trastuzumab or radiotherapy or would prevent prolonged follow-up
• No other malignancies unless patient has been disease-free ≥ 5 years and at low risk for recurrence, except for treated carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, or basal cell or squamous cell carcinoma of the skin

Outline

Patients are stratified according to menopausal status (pre- vs post-), plan for hormonal therapy (yes vs no), and nuclear grade (low or intermediate vs high). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo standard whole breast irradiation (WBI) over 5-6 weeks.
• Arm II: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in arm I.

Tumor tissue samples are analyzed for mRNA and DNA copy numbers of HER2, cMYC, and other candidate predictive genes; PI3K gene mutation status; other candidate predictors of trastuzumab response; and candidate prognostic markers of ductal carcinoma in situ.

After completion of study therapy, patients are followed every 6 months for 5 years and then every 12 months for 5 years.

If you are interested in this breast cancer research study, please contact:

Venita Alston Crawford, RN, BSN

Clinical Research Nurse Coordinator

crawfv@holycrosshealth.org

301-754-8556

Principal Investigator:
Linda M. Burrell, M.D., Medical Oncologist

(6) NSABP-B-47: Phase III Randomized Study of Adjuvant Chemotherapy With Versus Without Trastuzumab in Women With Node-Positive or High-Risk Node-Negative HER2-Low Invasive Breast Cancer

Primary Objectives: To determine whether the addition of trastuzumab to chemotherapy (TC or AC→WP) improves invasive disease-free survival (IDFS) in women with resected node-positive or high-risk node-negative breast cancer which is reported as HER2-low by all HER2 testing performed.

Entry Criteria 

Disease Characteristics:

• The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination
• All of the following staging criteria (according to the 7th edition of the AJCC Cancer Staging Manual) must be met:
  • By pathologic evaluation, primary tumor must be pT1-3
  • By pathologic evaluation, ipsilateral nodes must be pN0, pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN2b, pN3a, or pN3b
    • If pN0, one of the following criteria must be met:
      • pT2 and estrogen receptor (ER) negative and progesterone receptor (PgR) negative
      • pT2 and ER positive (PgR status may be positive or negative) and either grade 3 histology or Oncotype DX® Recurrence Score of ≥ 25
• No T4 tumors including inflammatory breast cancer
• No definitive clinical or radiologic evidence of metastatic disease
  •  [Note: Chest imaging (mandatory for all patients) and other imaging (if required) must have been performed within 90 days prior to randomization]
• No synchronous or previous contralateral invasive breast cancer (patients with synchronous and/or previous contralateral DCIS or LCIS are eligible)
• No previous ipsilateral invasive breast cancer or ipsilateral DCIS (patients with synchronous or previous ipsilateral LCIS are eligible)
• HER2 status of the primary tumor must be evaluated prior to randomization; all testing performed must indicate that the tumor is HER2-low as defined below:
  • The IHC staining results must indicate a score of 1+ (ISH testing is not required) or 2+ (FISH or CISH must also be performed and must indicate that the tumor is HER2-low as described below)
  • If ISH (FISH or CISH) testing is performed, test results must be as follows and IHC must be 1+ or 2+:
    • If FISH is performed, the ratio of HER2 to CEP17 must be < 2.0 or, if a ratio was not performed, the HER2 gene copy number must be < 4 per nucleus
    • If CISH is performed, the result must indicate a HER2 gene copy number of < 4 per nucleus
  •  [Note: If the IHC staining intensity is reported as a range, e.g., 0 to 1+ or 1+ to 2+, the higher intensity score in the range should be used to determine eligibility.]
• No primary tumor with any of the following HER2 testing results:
  • IHC staining intensity of 0 or 3+
  • FISH with a ratio of HER2 to CEP17 ≥ 2.0 or HER2 copy number ≥ 4 per nucleus
  • CISH result indicating HER2-positive or HER2 gene copy number ≥ 4 per nucleus
• The patient must have undergone either a total mastectomy or breast-conserving surgery (lumpectomy) (patients who have had a nipple-sparing mastectomy are eligible)
  • For patients who undergo lumpectomy, the margins of the resected specimen must be histologically free of invasive tumor and DCIS as determined by the local pathologist; if pathologic examination demonstrates tumor at the line of resection, additional operative procedures may be performed to obtain clear margins; if tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible (patients with margins positive for LCIS are eligible without additional resection)
  • For patients who undergo mastectomy, margins must be free of gross residual tumor (patients with microscopic positive margins are eligible as long as post-mastectomy RT of the chest wall will be administered)
  • The interval between the last surgery for breast cancer (treatment or staging) and randomization must be no more than 84 days
• The patient must have completed one of the procedures for evaluation of pathologic nodal status listed below:
  • Sentinel lymphadenectomy alone:
    • If pathologic nodal staging based on sentinel lymphadenectomy is pN0 or pN1b
    • If pathologic nodal staging based on sentinel lymphadenectomy is pN1mi or pN1a, the primary tumor must be T1 or T2 by pathologic evaluation and the nodal involvement must be limited to 1 or 2 positive nodes
  • Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes if the sentinel node (SN) is positive
  • Axillary lymphadenectomy with or without SN isolation procedures
• The patient must have ER analysis performed on the primary tumor prior to randomization; if ER analysis is negative, then PgR analysis must also be performed (either the core biopsy or surgical resection specimen can be used for ER/PgR testing); patients with a primary tumor that is hormone receptor-positive or receptor-negative are eligible

Prior/Concurrent Therapy:

• See Disease Characteristics
• No previous therapy with anthracyclines, taxanes, or trastuzumab for any malignancy
• No chemotherapy or HER2-targeted therapy administered for the currently diagnosed breast cancer prior to randomization
• No whole-breast RT prior to randomization or partial-breast RT that cannot be completed on or before the date of randomization
• No use of any investigational product within 30 days prior to randomization
• No continued endocrine therapy such as raloxifene or tamoxifen (or other SERM) or an aromatase inhibitor (patients are eligible if these medications are discontinued prior to randomization)
• No continued use of sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy (patients are eligible if these medications are discontinued prior to randomization)
• No chronic daily treatment with corticosteroids with a dose of ≥ 10 mg/day methylprednisolone equivalent (excluding inhaled steroids)
• No other concurrent chemotherapy
• No other concurrent targeted therapy for malignancy
• No partial-breast irradiation following randomization
• Concurrent participation in NSABP-B-39 allowed

Patient Characteristics:

• Pre- or postmenopausal
• ECOG performance status of 0 or 1
• ANC must be ≥ 1,200/mm³
• Platelet count must be ≥ 100,000/mm³
• Hemoglobin must be ≥ 10 g/dL
• Total bilirubin must be ≤ ULN for the lab unless the patient has a bilirubin elevation > ULN to 1.5 x ULN due to Gilbert disease or similar syndrome involving slow conjugation of bilirubin
• Alkaline phosphatase must be ≤ 2.5 x ULN for the lab
• AST must be ≤ 1.5 x ULN for the lab (if ALT is performed instead of AST [per institution's standard practice], the ALT value must be ≤ 1.5 x ULN; if both were performed, the AST must be ≤ 1.5 x ULN)
• Alkaline phosphatase and AST may not both be > the ULN
• Patients with AST or alkaline phosphatase > ULN are eligible for inclusion in the study if liver imaging (CT, MRI, PET-CT, or PET scan) performed within 90 days prior to randomization does not demonstrate metastatic disease and the above requirements are met
• Patients with alkaline phosphatase that is > ULN but ≤ 2.5 x ULN or unexplained bone pain are eligible for inclusion in the study if a bone scan, PET-CT scan, or PET scan performed within 90 days prior to randomization does not demonstrate metastatic disease
• The most recent postoperative serum creatinine performed within 6 weeks prior to randomization must be ≤ ULN for the lab
• Not pregnant or nursing
• Negative pregnancy test
• LVEF assessment must be performed within 90 days prior to randomization; LVEF assessment performed by 2-D echocardiogram is preferred, however, MUGA scan may be substituted based on institutional preferences
  • For patients who will receive the TC chemotherapy regimen, the LVEF must be ≥ 50% regardless of the cardiac-imaging facility's lower limit of normal
  • For patients who will receive the AC→WP chemotherapy regimen, the LVEF must be ≥ 55% regardless of the cardiac-imaging facility's lower limit of normal
  •  [Note: Since the pre-entry LVEF serves as the baseline for comparing subsequent LVEF assessments, it is critical that this baseline study be an accurate assessment. If the baseline LVEF is > 70%, the investigator is encouraged to have the accuracy of the initial LVEF result confirmed and repeat the test if the accuracy is uncertain.]
• No history of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to randomization
• No cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens, including, but not limited to:
  • Active cardiac disease:
    • Angina pectoris that requires the current use of anti-anginal medication
    • Ventricular arrhythmias except for benign premature ventricular contractions
    • Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
    • Conduction abnormality requiring a pacemaker
    • Valvular disease with documented compromise in cardiac function
    • Symptomatic pericarditis
  • History of cardiac disease:
    • Myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LV function
    • History of documented CHF
    • Documented cardiomyopathy
• No hypertension defined according to the following ineligibility criteria:
  • For patients who will receive TC (regardless of the patient's age): uncontrolled hypertension defined as sustained systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg (patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria)
  • For patients < 50 years old who will receive AC→WP: uncontrolled hypertension defined as sustained systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg (patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria)
  • For patients ≥ 50 years old who will receive AC→WP: uncontrolled hypertension defined as sustained systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg OR controlled hypertension (systolic BP ≤ 150 mm Hg and ≤ 90 mmHg), if anti-hypertensive medication(s) are needed
  •  [Note: Patients who are not eligible based on the AC→WP regimen BP criteria but who meet the TC regimen BP criteria are eligible for B-47 if the intended chemotherapy regimen is changed to TC.]
• No active hepatitis B or hepatitis C with abnormal liver function tests
• No intrinsic lung disease resulting in dyspnea
• No poorly controlled diabetes mellitus
• No active infection or chronic infection requiring chronic suppressive antibiotics
• No nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory neuropathy) ≥ grade 2, per the CTCAE v4.0
• No conditions that would prohibit administration of corticosteroids
• No known hypersensitivity to any of the study drugs or excipients, e.g., polysorbate 80 and Cremophor® EL
• No other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up
• No psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements

Outline

This is a multicenter study. Patients are stratified according to IHC score (1+ vs 2+), number of positive nodes (0-3 vs 4-9 vs 10+), hormone receptor status (ER-positive and/or PgR-positive vs ER- and PgR-negative), and intended chemotherapy regimen* (docetaxel and cyclophosphamide vs doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel). Patients are randomized to 1 of 2 treatment arms.

 [Note: *Chemotherapy regimen is based on the investigator's preference.]

• Arm I:
  • Group A: Patients receive docetaxel IV over 60 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 6 courses.
  • Group B: Patients receive doxorubicin hydrochloride IV over 15 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 2 or 3 weeks (at the investigator's discretion) for 4 courses. Patients then receive paclitaxel IV over 60 minutes once weekly for 12 doses.
• Arm II:
  • Group A: Patients receive chemotherapy as in arm IA. Patients also receive trastuzumab IV over 30-90 minutes on day 1. Trastuzumab treatment repeats every 3 weeks for 11 courses.
  • Group B: Patients receive chemotherapy as in arm IB. Patients also receive trastuzumab IV over 30-90 minutes weekly for 12 doses. After completion of paclitaxel, patients receive trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for 12 courses.

Tumor and blood samples may be collected periodically during study treatment for correlative studies.

After completion of study treatment, patients are followed up every 6 months for 5 years and then every 12 months for 5 years. 

If you are interested in this breast cancer research study, please contact:

Venita Alston Crawford, RN, BSN

Clinical Research Nurse Coordinator

crawfv@holycrosshealth.org

301-754-8556

Principal Investigator:
Cheryl A. Aylesworth, M.D., Medical Oncologist

(7) NSABP-B-39: A Randomized Phase III Study of Conventional Whole Breast Irradiation (WBI) Versus Partial Breast Irradiation (PBI) for Women with Stage 0, I, or II Breast Cancer

Primary Objectives: Compare local tumor control in women with ductal carcinoma in situ or stage I or II breast cancer treated with adjuvant whole breast vs partial breast irradiation following lumpectomy.

Entry Criteria 

Disease Characteristics:

• Histologically confirmed ductal carcinoma in situ (DCIS*) or invasive* adenocarcinoma of the breast
  • Stage 0, I, or II disease
    • Stage II tumors must be ≤ 3 cm
  • Gross disease must be unifocal
    • Microscopic multifocality allowed provided total pathological tumor size is ≤ 3 cm
  • No proven multicentric carcinoma in more than 1 quadrant or separated by ≥ 4 cm
  • No non-epithelial breast malignancies (e.g., sarcoma or lymphoma)

 [Note: *Patients who are 50 years of age and over with DCIS regardless of hormone receptor status AND patients with invasive breast cancer meeting all of the following criteria: ≥ 50 years of age, node-negative, and hormone-receptor positive status will not be enrolled in study after 12/30/2006]

• Prior axillary staging required for patients with invasive breast cancer, including 1 of the following:
  • Sentinel node biopsy alone (if sentinel node is negative)
  • Sentinel node biopsy followed by axillary dissection or sampling with ≥ 6 axillary nodes (if sentinel node is positive)
  • Axillary dissection alone with ≥ 6 axillary nodes
• No more than 3 positive axillary nodes
  • No axillary nodes with definite evidence of microscopic or macroscopic extracapsular extension
  • No positive non-axillary sentinel nodes (intramammary nodes are staged as axillary nodes)
  • No palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes unless there is histologic confirmation that these nodes are negative for tumor
• Must have undergone lumpectomy
  • Resected margins histologically free of tumor
  • Re-excision of surgical margins allowed
  • Target lumpectomy cavity clearly delineated AND target lumpectomy/whole breast reference volume ≤ 30% based on postoperative pre-randomization CT scan
  • Final surgery (i.e., lumpectomy, re-excision of margins, or axillary staging procedure) within the past 42 days
• No suspicious microcalcifications, densities, or palpable abnormalities in the ipsilateral or contralateral breast unless biopsied and found to be benign
• No Paget’s disease of the nipple
• No history of invasive breast cancer or DCIS
  • Prior lobular carcinoma in situ treated by surgery alone allowed
• No synchronous bilateral invasive or non-invasive breast cancer
• Partial breast irradiation deemed technically deliverable by radiation oncologist at a credentialed facility
• Must have undergone a history and physical exam within the past 4 months AND a bilateral mammogram within the past 6 months
• Hormone receptor status:
  • Estrogen receptor (ER) status known
  • Progesterone status known if ER analysis is negative
  • Marginal or borderline results are considered positive

Prior/Concurrent Therapy:

Biologic therapy

• No prior biologic therapy for this malignancy

Chemotherapy

• No prior chemotherapy for this malignancy
• No concurrent chemotherapy during study radiotherapy

Endocrine therapy

• No prior hormonal therapy for this malignancy unless total duration of hormonal therapy was no more than 28 days before randomization
• Concurrent hormonal therapy allowed provided it is not administered during chemotherapy
• No concurrent raloxifene, tamoxifen, or other selective estrogen receptor modulating drugs
• No concurrent hormone replacement therapy
• No concurrent Femring^®

Radiotherapy

• No prior radiotherapy for this malignancy
• No prior breast or thoracic radiotherapy
• No concurrent brachytherapy boosts
• No concurrent intensity modulated radiotherapy
• No concurrent regional nodal irradiation

Surgery

• See Disease Characteristics
• No prior breast implants
  • Patients who have had implants removed are eligible

Other

• No other concurrent anticancer therapy

Patient Characteristics:

Age

• 18 and over

Sex

• Female

Menopausal status

• Premenopausal or postmenopausal

Performance status

• Not specified

Life expectancy

• At least 10 years, excluding diagnosis of breast cancer

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective non-hormonal contraception
• No other malignancy within the past 5 years except previously treated carcinoma in situ of the cervix or colon, melanoma in situ, or basal cell or squamous cell skin cancer
  • Deemed to be at low risk for recurrence
• No collagen vascular disease (e.g., systemic lupus erythematosus or scleroderma), specifically dermatomyositis with a CPK level above normal, or active skin rash
• No psychiatric or addictive disorder that would preclude study therapy

Outline

This is a randomized, multicenter study. Patients are stratified according to disease stage (ductal carcinoma in situ [DCIS] only vs invasive and node negative vs invasive with 1-3 positive nodes), menopausal status (premenopausal vs postmenopausal), hormone receptor status (estrogen receptor [ER]-positive and/or progesterone receptor [PR]-positive vs ER-negative and PR-negative), intention to receive chemotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms. (Patients who are 50 years of age and over with DCIS regardless of hormone receptor status AND patients with invasive breast cancer meeting all of the following criteria: ≥ 50 years of age, node-negative, and hormone-receptor positive status will not be enrolled in study after 12/30/2006.)

• Arm I: Patients undergo whole-breast irradiation (WBI) once daily, 5 days a week, for 5-7 weeks.
• Arm II: Patients undergo partial-breast irradiation (PBI) twice daily on 5 days over a period of 5-10 days. This may be delivered by intracavitary brachytherapy or 3-D conformal radiotherapy.

Patients in both arms may receive adjuvant chemotherapy at least 2 weeks prior to initiation of WBI OR at least 2 weeks after completion of PBI at the discretion of the treating physician. Patients with ER-positive or PR-positive tumors may also receive hormonal therapy, beginning 3-12 weeks after completion of adjuvant chemotherapy (or before, during, or after completion of WBI or PBI for patients not receiving adjuvant chemotherapy) and continuing for at least 5 years.

After completion of study treatment, patients are followed at 1 and 6 months, every 6 months for 4.5 years, and then annually thereafter. 

If you are interested in this breast cancer research study, please contact:

Venita Alston Crawford, RN, BSN

Clinical Research Nurse Coordinator

crawfv@holycrosshealth.org

301-754-8556

Principal Investigator:
Sheela Modin, MD, Medical Oncologist

(8) CALGB-40503: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Endocrine Therapy Alone or Endocrine Therapy Plus Bevacizumab (NSC 704865; IND 7921) for Women with Hormone Receptor-Positive Advanced Breast Cancer

Primary Objectives: To compare the progression-free survival of women with estrogen- and/or progesterone-receptor-positive stage IIIB-IV breast cancer treated with letrozole with vs without bevacizumab as first-line treatment.

Entry Criteria 

Disease Characteristics:

• Histologic confirmation of invasive cancer of the female breast in either the primary or metastatic setting
  • Stage IIIB disease not amenable to local therapy or stage IV disease
• Must have measurable or nonmeasurable disease by RECIST criteria, with radiologic scans (CT scan of the chest/abdomen)
  • Measurable disease is defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 2.0 cm with conventional techniques or as ≥ 1.0 cm with spiral CT scan
  • Nonmeasurable disease is defined as all other lesions, including small lesions (longest diameter < 2.0 cm with conventional techniques or < 1.0 cm with spiral CT scan) and truly nonmeasurable lesions, including any of the following:
    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Inflammatory breast disease
    • Abdominal masses that are not confirmed and followed by imaging techniques
    • Cystic lesions
• Baseline bone scans required for all patients for determination of metastatic bone disease
  • CT scan with bone windows required only for patients with bone metastases as the only site of disease
• No known CNS metastases or leptomeningeal disease (screening with brain imaging is not required for asymptomatic patients)
• Hormone receptor status: tumors (from either primary or metastatic sites) must express estrogen receptor (ER) and/or progesterone receptor (PgR) in ≥ 1% of cells

Prior/Concurrent Therapy:

• No prior endocrine therapy in the metastatic setting unless tamoxifen or an aromatase inhibitor was initiated within 4 weeks prior to registration
  • If prior endocrine therapy was initiated within the past 4 weeks, the patients should remain on that chosen hormonal therapy (tamoxifen or aromatase inhibitor) as the study therapy  [Note: As of 5/15/2011, patients only receive letrozole.]
  • Patients who began therapy with tamoxifen (after 5/15/2011), anastrozole or exemestane must switch to letrozole
• Prior endocrine therapy in the adjuvant setting allowed
• Prior treatment with ovarian suppression is allowed in either the adjuvant or metastatic setting
  • If medical ovarian suppression is being administered it can be initiated any time prior to or at the start of protocol therapy, and continued throughout the duration of the trial
• At least 28 days since surgical castration with bilateral oophorectomy
• At least 2 weeks since prior radiotherapy and all toxicities resolved
• At least 12 months since the completion of prior adjuvant or neoadjuvant chemotherapy and all toxicities must have resolved
• No prior anti-VEGF or VEGFR tyrosine kinase inhibitor therapy
• May have received 1 prior chemotherapy regimen for metastatic disease
• More than 28 days since prior major surgical procedure or open biopsy and fully recovered from any such procedure
• No core biopsy or other minor surgical procedure (except placement of a vascular access device) within 7 days prior to study registration
• Prior palliative irradiation of a symptomatic lesion, or one that may produce disability (e.g., unstable femur) prior to study initiation, provided other measurable or non-measurable disease is present, is allowed
• Palliative radiotherapy may not be administered during protocol therapy
• Must not have anticipation of need for major surgical procedure during the course of the study
• Concurrent full-dose anticoagulation therapy is allowed for the treatment of prior conditions such as venous thromboses or atrial fibrillation, but not for the treatment of prior arterial thrombotic events
  • Patients on full-dose anticoagulants must be on a stable dose of warfarin and have an in-range INR (usually between 2 and 3) or be on a stable dose of low molecular weight heparin
• Concurrent antiplatelet agents, daily prophylactic aspirin, or anticoagulation for atrial fibrillation allowed
• Concurrent treatment with bisphosphonates is allowed and recommended
• No concurrent hormones or other chemotherapeutic agents except for steroids given for adrenal failure or chronic non-cancer related diseases, hormones administered for non-disease-related conditions (e.g., insulin for diabetes), and intermittent use of dexamethasone as an antiemetic in solid tumor protocols

Patient Characteristics:

• Menopausal status: pre- or postmenopausal, meeting 1 of the following criteria:
  • Age ≥ 55 years and one year or more of amenorrhea
  • Age < 55 years and one year or more of amenorrhea, with an estradiol assay < 20 pg/ml
  • Age < 55 with prior hysterectomy but intact ovaries, with an estradiol assay < 20 pg/ml
  • Surgical menopause with bilateral oophorectomy
  • Ovarian suppression on a luteinizing hormone-releasing hormone agonist (goserelin acetate or leuprolide acetate)
    • Premenopausal women must undergo ovarian suppression prior to beginning protocol therapy
      • Ovarian radiation is not permitted for induction of ovarian suppression
• ECOG (Zubrod) performance status 0-1
• Life expectancy ≥ 12 weeks
• Granulocytes ≥ 1,000/μl
• Platelet count ≥ 100,000/μl
• Creatinine ≤ 2.0 mg/dL
• Bilirubin ≤ 1.5 times upper limit of normal (ULN) unless due to Gilbert’s syndrome
• Transaminases (ALT, AST) ≤ 2.5 times ULN
• INR ≤ 1.6 unless on full dose warfarin
• Urinalysis ≤ 1+ protein
  • Proteinuria ≥ 2 + at baseline must demonstrate < 1 g of protein/24 hr or protein:creatinine ratio < 1 on 24-hour urine collection
• No “currently active” second malignancy other than nonmelanoma skin cancers
  • Patients are not considered to have a “currently active” malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse
• Taxane-related neurotoxicity must have resolved to sensory grade < 2
• No motor neuropathy of any grade
• No significant traumatic injury within 28 days prior to study registration
• No history of abdominal fistula, or intra-abdominal abscess within the past 6 months
• No history of GI perforation within the past 12 months
• No history of significant bleeding episodes (e.g., hemoptysis, upper or lower GI bleeding) within the past 6 months
• No clinically significant cardiovascular disease, including any of the following:
  • Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg and/or diastolic BP > 90 mm Hg on antihypertensive medications
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • Myocardial infarction or unstable angina within past 6 months
  • New York Heart Association class II-IV congestive heart failure
  • Symptomatic peripheral vascular disease
  • Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
  • Significant arterial thrombotic events
• No history of stroke or transient ischemic attack within the past 6 months
• History of seizures must be well controlled with standard medication
• No known allergies to imidazole drugs, (e.g., clotrimazole, ketoconazole, miconazole, econazole, sulconazole, ticonazole, or terconazole) or compounds structurally similar to bevacizumab (for patients treated with aromatase inhibitors)
• No known allergies to selective estrogen receptor modulators (e.g., tamoxifen, raloxifene, or toremifene) or compounds structurally similar to bevacizumab (for patients treated with tamoxifen)  [Note: As of 5/15/2011, patients only receive letrozole.]
• No serious, non-healing wound, ulcer, or bone fracture
• Not pregnant or nursing
• Negative pregnancy test

Outline

This is a multicenter study. Patients are stratified according to planned endocrine therapy* (letrozole vs tamoxifen*), disease measurability (no vs yes), and disease-free interval from initial diagnosis to first progression (≤ 24 months vs > 24 months). Patients are randomized to 1 of 2 treatment arms. [Note: The placebo-controlled portion of the study was canceled on 5-15-10]

• Arm I: Patients receive oral endocrine therapy* (tamoxifen citrate or letrozole) once daily on days 1-21 and bevacizumab IV on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive oral endocrine therapy* (tamoxifen citrate or letrozole) once daily on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 6 months for the first 2 years and then annually for up to 3 years.

 [Note: *As of 5/15/2011, patients only receive letrozole.]

If you are interested in this breast cancer research study, please contact:

Venita Alston Crawford, RN, BSN

Clinical Research Nurse Coordinator

crawfv@holycrosshealth.org

301-754-8556

Principal Investigator:
Cheryl A. Aylesworth, M.D., Medical Oncologist

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