Metronomic Chemotherapy in Combination With Bevacizumab for Advanced Breast Cancer
18 Years
N/A
Female
Breast Cancer
Trial Information
Metronomic Chemotherapy in Combination With Bevacizumab for Advanced Breast Cancer
OBJECTIVES:
Primary
- Compare the overall response rate in women with metastatic breast cancer treated with
metronomic low-dose cyclophosphamide and methotrexate with or without bevacizumab.
Secondary
- Compare the progression-free survival of patients treated with these regimens.
- Compare the toxicity of these regimens in these patients.
- Correlate markers of angiogenesis, including vascular endothelial growth factor and
circulating endothelial cells, at baseline and during treatment, with response in
patients treated with these regimens.
OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive low-dose oral cyclophosphamide once daily on days 1-28,
low-dose oral methotrexate twice daily on days 1, 2, 8, 9, 15, 16, 22 and 23, and
bevacizumab IV over 30-90 minutes on days 1 and 15.
- Arm II: Patients receive cyclophosphamide and methotrexate as in arm I. In both arms,
courses repeat every 28 days in the absence of disease progression or unacceptable
toxicity.
Patients in arm II who have progressive disease have the option of discontinuing treatment
or crossing over to arm I.
PROJECTED ACCRUAL: A total of 36-66 patients (18-33 per treatment arm) will be accrued for
this study within 7-12 months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed invasive breast cancer
- Metastatic (stage IV) disease confirmed by histology or cytology, physical exam,
or radiologic study
- Measurable disease
- At least one unidimensionally measurable lesion at least 20 mm by conventional
techniques OR at least 10 mm by spiral CT scan
- Measurable lesions in a previously irradiated field must have progressed after
radiotherapy
- HER2-positive patients must have received prior trastuzumab (Herceptin^®) for
advanced disease or in the adjuvant setting
- No evidence of brain metastases by brain CT scan or MRI
- Hormone receptor status:
- Not specified
PATIENT CHARACTERISTICS:
Age
- 18 and over
Sex
- Female
Menopausal status
- Not specified
Performance status
- ECOG 0-1 OR
- Karnofsky 70-100%
Life expectancy
- More than 6 months
Hematopoietic
- Absolute neutrophil count ≥ 1,000/mm^3
- Platelet count ≥ 100,000/mm^3
- No bleeding diatheses (including hemoptysis)
Hepatic
- AST and ALT ≤ 4.0 times upper limit of normal (ULN)
- Bilirubin ≤ 2 times ULN
Renal
- Creatinine ≤ 2.0 mg/dL
- Urinary protein < 500 mg/24-hour-urine collection OR
- Protein urinalysis < 1+
Cardiovascular
- LVEF ≥ 50% by echocardiogram or nuclear medicine gated study
- No poorly controlled hypertension
- No prior blood clots
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of grade 3 or 4 allergic reaction to compounds of similar chemical or
biological composition to cyclophosphamide or methotrexate
- No concurrent uncontrolled illness
- No active or ongoing infection
- No psychiatric illness or social situation that would preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- No prior experimental angiogenesis inhibitors
- No concurrent filgrastim (G-CSF)
- Concurrent epoetin alfa growth factor support allowed
Chemotherapy
- Prior adjuvant chemotherapy for early-stage breast cancer allowed, including
cyclophosphamide-based chemotherapy
- No more than 1 prior chemotherapy regimen for metastatic breast cancer
- No prior oral cyclophosphamide- or methotrexate-based therapy for metastatic disease
Endocrine therapy
- Prior hormonal therapy in the adjuvant or metastatic setting or for early-stage
breast cancer allowed
- No concurrent hormonal therapy, including luteinizing hormone-releasing hormone
agonists
Radiotherapy
- See Disease Characteristics
- Prior radiotherapy in the metastatic or early-stage setting allowed
- Concurrent radiotherapy allowed
Surgery
- More than 28 days since prior surgery except for venous access device or diagnostic
study
Other
- Recovered from prior therapy
- No concurrent anticoagulation or chronic aspirin therapy (> 325 mg/day)
- Concurrent low-dose anticoagulation or thrombolytic agents for venous access
patency allowed
- No other concurrent investigational or experimental therapy
- No other concurrent anticancer agents or therapies
- Concurrent bisphosphonates allowed provided skeletal sites are not the primary sites
used in assessing response
- If skeletal sites are being followed for measurable response, bisphosphonates
must be initiated at least 4 weeks before study entry
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Primary Purpose: Treatment
Outcome Measure:
Clinical response rate (complete and partial) as measured by RECIST criteria
Safety Issue:
No
Principal Investigator
Harold J. Burstein, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Dana-Farber Cancer Institute
Authority:
United States: Federal Government
Study ID:
CDR0000361807
NCT ID:
NCT00083031
Start Date:
November 2002
Completion Date:
Related Keywords:
- Breast Cancer
- recurrent breast cancer
- stage IV breast cancer
- Breast Neoplasms
Name | Location |
|---|---|
| Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston, Massachusetts 02115 |
