Status:
COMPLETED
Bevacizumab and Letrozole in Treating Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer That Cannot Be Removed By Surgery
Lead Sponsor:
University of California, San Francisco
Collaborating Sponsors:
National Cancer Institute (NCI)
Memorial Sloan Kettering Cancer Center
Conditions:
Breast Cancer
Eligibility:
FEMALE
18-120 years
Phase:
PHASE2
Brief Summary
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with th...
Detailed Description
OBJECTIVES: Primary * Determine the safety and feasibility of bevacizumab in combination with letrozole in postmenopausal women with estrogen receptor- and/or progesterone receptor-positive, unresec...
Eligibility Criteria
Inclusion
- DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed carcinoma of the breast
- Locally advanced or metastatic (stage IV) disease
- Unresectable disease
- Measurable or nonmeasurable disease
- May have had stable or progressive disease after ≤ 2 prior conventional chemotherapy regimens for treatment of locally advanced or metastatic breast cancer
- Prior chemotherapy in the adjuvant or metastatic setting is not required
- Any number of prior neoadjuvant or adjuvant chemotherapy regimens allowed
- Prior treatment with high-dose chemotherapy and autologous stem cell or bone marrow transplantation is considered 1 regimen when administered for metastatic disease (including induction chemotherapy and preparative regimen)
- May have had stable or responding disease on prior nonsteroidal aromatase inhibitors (e.g., letrozole, anastrozole, or aminogluthemide)
- Any prior aromatase inhibitor-related toxicity ≥ grade 3 must have resolved ≥ 4 weeks before the start of study treatment
- May have had disease progression on other prior hormonal therapy (e.g., selective estrogen receptor modulators \[SERMs\], receptor downregulators \[SERDs\], or ovarian suppression) in the adjuvant or metastatic setting
- No history or evidence of primary brain tumor or brain metastases by CT scan or MRI
- Must have estrogen receptor- and/or progesterone receptor-positive tumor
- PATIENT CHARACTERISTICS:
- Rendered postmenopausal with ovarian suppression (ovarian suppression with a depot LH-RH agonist allowed) prior to the start of study treatment OR is already postmenopausal, as defined by 1 of the criteria:
- No spontaneous menses for ≥ 12 months if the patient is ≥ 50 years old
- Amenorrheic for ≥ 12 months if the patient is \< 50 years old, with serum estradiol and follicle-stimulating hormone (FSH) levels within the institutional postmenopausal range
- Bilateral oophorectomy
- At least 28 days since surgical oophorectomy
- Patients who have had prior hysterectomy but intact ovaries must be ≥ 55 years old, or have serum estradiol and FSH levels within the postmenopausal range
- Ongoing ovarian suppression with a depot LH-RH agonist
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- Life expectancy \> 3 months
- Female only
- Absolute neutrophil count ≥ 1,000/mm\^3
- Platelet count ≥ 75,000/mm\^3
- WBC ≥ 2,500/mm\^3
- AST and ALT ≤ 2.5 times upper limit of normal
- Bilirubin normal
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- No proteinuria at baseline
- Patients who unexpectedly have ≥ +1 proteinuria must undergo a 24-hour urine collection that demonstrates ≤ 500 mg of protein over 24 hours
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No presence of bleeding diathesis or coagulopathy
- No history of allergic reaction to compounds of similar chemical or biologic composition to letrozole or bevacizumab
- No serious, nonhealing wound, ulcer, or bone fracture
- No unstable angina pectoris
- No serious cardiac arrhythmia requiring medication
- No uncontrolled hypertension
- No myocardial infarction
- No New York Heart Association class II-IV congestive heart failure
- No peripheral vascular disease ≥ grade II within the past year
- No other clinically significant cardiovascular disease
- No history or evidence of other CNS disease by CT scan or MRI, including seizures not controlled with standard medical therapy or stroke
- No gastrointestinal tract disease resulting in an inability to take oral medication
- No requirement for IV alimentation
- No significant traumatic injury within the past 28 days
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled intercurrent illness
- PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior steroidal aromatase inhibitors (e.g., exemestane) unless administered in the adjuvant setting (not for metastatic disease) and ≥ 12 months have elapsed since last treatment
- Any number of prior immunotherapies (e.g., trastuzumab \[Herceptin\^®\] or vaccines) in the adjuvant or metastatic setting allowed
- More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
- More than 3 weeks since prior radiotherapy
- More than 3 weeks since prior immunotherapy
- More than 3 weeks since prior investigational therapy
- More than 2 weeks since prior hormonal therapy except letrozole therapy or a luteinizing hormone-releasing hormone (LH-RH) agonist for ovarian suppression
- No prior surgical procedures affecting absorption
- More than 28 days since prior major surgery or open biopsy
- At least 24 hours since prior placement of indwelling catheters
- At least 10 days since prior and no concurrent full-dose oral or parenteral anticoagulants or thrombolytic agents except as required to maintain patency of preexisting, permanent indwelling IV catheters
- Patients receiving warfarin should have INR \< 1.5
- No prior bevacizumab
- No other prior KDR inhibitors (e.g., vascular endothelial growth factor \[VEGF\] Trap, SU5416, SU6668, ZD6474, vatalanib, AEE788, or IMC-1CII)
- No other concurrent investigational agent
- No concurrent chronic daily treatment with aspirin (\> 325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit platelet function (e.g., cyclooxygenase-1 inhibitors)
- Concurrent bisphosphonates (e.g., zoledronate or pamidronate) or growth factors allowed
- No other concurrent anticancer agents or therapies
Exclusion
Key Trial Info
Start Date :
August 1 2004
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 24 2016
Estimated Enrollment :
43 Patients enrolled
Trial Details
Trial ID
NCT00305825
Start Date
August 1 2004
End Date
May 24 2016
Last Update
August 31 2017
Active Locations (2)
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1
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115-1710
2
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021