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Endocrine Therapy With or Without Anti-VEGF Therapy: A Randomized, Phase III Trial of Endocrine Therapy Alone or Endocrine Therapy Plus Bevacizumab (NSC 704865; IND 7921) for Women With Hormone Recept

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Trial Conditions
  • Estrogen Receptor-positive Breast Cancer
  • Breast Cancer
  • Progesterone Receptor-positive Breast Cancer
  • Recurrent Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IV Breast Cancer
What is the purpose of this trial?

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen* or letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether giving hormone therapy is more effective with or without bevacizumab in treating advanced breast cancer. PURPOSE: This randomized phase III trial is studying giving tamoxifen* or letrozole together with bevacizumab to see how well it works compared with tamoxifen* or letrozole alone in treating women with stage III or stage IV breast cancer.

Date & Status

Active, not recruiting

Who can Participate?

Eligibility

Ages:
18 and older

Gender:
Female

Eligibility

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

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

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

Gender: Female
Steward Physician(s)
  • Maura Dickler
Facilities
  • Holy Family Hospital - Active, not recruiting
Trial Interventions
Biological
  • bevacizumab
Drug
  • tamoxifen citrate
  • letrozole
Other
  • laboratory biomarker analysis
  • questionnaire administration
Physician Researcher

Investigator Name:

  • Maura Dickler

Other Information

Sponsor: Cancer and Leukemia Group B
Phase: Phase 3
Trial ID: NCT00601900
Volunteers:  Not Accepting Healthy Volunteers

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