Docetaxel, Capecitabine, and Bevacizumab in Treating Patients With Metastatic Breast Cancer

Alliance for Clinical Trials in Oncology

Status and phase

Completed

Phase 2

Conditions

Breast Cancer

Treatments

Drug: capecitabine

Biological: bevacizumab

Drug: docetaxel

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00088998

CDR0000377886 (Registry Identifier)

NCCTG-N0432

NCI-2012-02617 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as docetaxel and capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as bevacizumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Bevacizumab may also stop the growth of tumor cells by stopping blood flow to the tumor. Combining chemotherapy with monoclonal antibody therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving docetaxel and capecitabine together with bevacizumab works in treating patients with metastatic breast cancer.

Full description

OBJECTIVES:

Primary

Determine the response rate in patients with metastatic breast cancer treated with docetaxel, capecitabine, and bevacizumab as first-line chemotherapy.

Secondary

Determine time to disease progression in patients treated with this regimen.
Determine survival of patients treated with this regimen.
Determine the toxicity profile of this regimen in these patients.
Determine the duration of response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive docetaxel IV over 1 hour and bevacizumab IV over 30-90 minutes on day 1. Patients also receive oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive at least 2 additional courses beyond CR.

Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.

Enrollment

46 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed invasive breast cancer
- Clinical evidence of metastatic disease
  - No bone metastases as the only evidence of metastasis
Measurable disease
- At least 1 lesion ≥ 2.0 cm by CT scan or MRI OR ≥ 1.0 cm by spiral CT scan
  - Lesions on chest x-ray allowed provided they are clearly defined and surrounded by aerated lung
- Clincal lesions only considered measurable when they are superficial (e.g., skin nodules or palpable lymph nodes)
- Target lesion must not have been exposed to prior radiotherapy unless disease has progressed since completion of radiotherapy
- The following are not considered measurable disease:
  - Bone lesions
  - Leptomeningeal disease
  - Ascites
  - Pleural or pericardial effusion
  - Inflammatory breast disease
  - Lymphangitis cutis or pulmonis
  - Abdominal masses that are not confirmed and followed by imaging techniques
  - Cystic lesions
No HER2/neu-positive tumors by immunohistochemistry or amplified fluorescence in situ hybridization unless disease has progressed after trastuzumab (Herceptin®)-containing therapy alone or with antiestrogen hormonal therapy for metastatic disease OR trastuzumab is contraindicated
Prior breast cancer allowed
No prior or active brain metastases
Hormone receptor status:
- Not specified

PATIENT CHARACTERISTICS:

Age

18 and over

Sex

Male or female

Menopausal status

Not specified

Performance status

ECOG 0-1

Life expectancy

At least 3 months

Hematopoietic

Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 8.0 g/dL
No bleeding diathesis or uncontrolled coagulopathy

Hepatic

Bilirubin normal
Meets 1 of the following criteria:
- AST and ALT normal AND alkaline phosphatase ≤ 5 times upper limit of normal (ULN)
- AST and ALT ≤ 1.5 times ULN AND alkaline phosphatase ≤ 2.5 times ULN
- AST and ALT ≤ 5 times ULN AND alkaline phosphatase normal

Renal

Creatinine clearance ≥ 30 mL/min
No proteinuria OR
Protein < 1 g by 24-hour urine collection
No nephrotic syndrome

Cardiovascular

No uncontrolled hypertension (i.e., blood pressure > 160/90 mm Hg on ≥ 2 different observations ≥ 5 minutes apart)
- Blood pressure < 140/90 mm Hg on ≥ 3 different observations over ≥ 14 days, for patients who recently began or adjusted anti-hypertensive medication
No atrial or venous thrombosis within the past month
No clinically significant heart disease, including any of the following:
- Congestive heart failure
- Symptomatic coronary artery disease
- Uncontrolled cardiac arrhythmias
- Unstable angina
No myocardial infarction within the past 12 months
No history of cerebrovascular accident

Pulmonary

No hemoptysis within the past 6 months

Gastrointestinal

No lack of physical integrity of the upper gastrointestinal tract
No malabsorption syndrome
Able to receive oral medication

Other

No other stage III or IV invasive malignancy requiring treatment within the past 5 years
No pre-existing peripheral neuropathy > grade 1
No history of allergy or hypersensitivity to study drugs, agents that are chemically similar to study drugs, or drugs that contain polysorbate 80
No prior severe reaction to fluoropyrimidines
No known hypersensitivity to fluorouracil
No known dihydropyrimidine dehydrogenase deficiency
No active infection
No significant medical condition that would preclude study participation
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 30 days after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics
No other concurrent biologic therapy

Chemotherapy

Prior adjuvant or neoadjuvant chemotherapy allowed for primary disease
No prior chemotherapy for metastatic disease
More than 4 weeks since prior cytotoxic chemotherapy
More than 6 months since prior taxanes (e.g., docetaxel or paclitaxel)
No other concurrent chemotherapy

Endocrine therapy

See Disease Characteristics
Prior antiestrogen hormonal therapy allowed in the adjuvant or metastatic setting

Radiotherapy

See Disease Characteristics
More than 4 weeks since prior radiotherapy to a target lesion
- Prior single-dose palliative radiotherapy allowed within the past 4 weeks
No concurrent radiotherapy

Surgery

More than 4 weeks since prior major surgery

Other

More than 2 weeks since prior aspirin, anticoagulants, or thrombolytic agents
- Concurrent low-dose warfarin (1 mg/day) to maintain patency of vascular access device allowed
More than 4 weeks since prior investigational agents
No concurrent aspirin, anticoagulants, or thrombolytic agents
No concurrent participation in another clinical trial involving investigational agents or procedures