Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer

University College London Hospitals NHS Foundation Trust (UCLH)

Status and phase: Completed; Phase 2

Conditions: Breast Cancer; brca2 Mutation Carrier; Hereditary Breast/Ovarian Cancer (brca1, brca2); brca1 Mutation Carrier

Treatments: Drug: docetaxel; Drug: carboplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT00321633

EUDRACT-2004-001496-20

CDR0000467994

BBC-CRUK-BRCA-TRIAL

CRUK-BRCA-TRIAL

ISRCTN43372330

EU-20603

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as carboplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether carboplatin is more effective than docetaxel in treating patients with metastatic genetic breast cancer.

PURPOSE: This randomized phase II trial is studying carboplatin to see how well it works compared to docetaxel in treating women with metastatic genetic breast cancer.

Full description

OBJECTIVES:

Primary

• Compare the safety and effectiveness of carboplatin vs docetaxel in women with metastatic breast cancer and the BRCA1 or BRCA2 gene mutation.

Secondary

• Compare time to disease progression in patients treated with these regimens.
• Compare progression-free survival of patients treated with carboplatin vs docetaxel.

OUTLINE: This is a randomized, open-label, multicenter, pilot study. Patients are stratified according to gene mutation (BRCA1 vs BRCA2), prior adjuvant taxane chemotherapy (yes vs no), liver or lung metastasis affecting the parenchyma (yes vs no), Jewish ancestry by parent or grandparent (yes vs no), and first-line treatment vs second-line treatment. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive carboplatin IV over 1 hour on day 1.
• Arm 2: Patients receive docetaxel IV over 1 hour on day 1. In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression after 3 or 6 courses of treatment may crossover to the alternative treatment arm. If progression is present after 3 courses in the crossover arm, patients may receive further treatment at the discretion of their oncologist. Patients responding to and tolerating treatment well, may be given 2 further courses in accordance with local center policy, although this is not encouraged.

Patients with HER2-positive disease may receive trastuzumab (Herceptin®) IV once every 7 or 21 days.

After completion of study treatment, patients are followed periodically for survival.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 148 patients will be accrued for this study.

Enrollment: 148 estimated patients

Sex: Female

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer

  • BRCA1 or BRCA2 mutation carrier
  • Metastatic disease

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan

• Stable, treated brain metastases allowed provided other sites of measurable disease are present

• Patients with bone metastases who are currently receiving bisphosphonates for palliation are eligible provided other sites of measurable disease are present

• Patients who have not received anthracycline-based chemotherapy in the adjuvant setting may receive a non-taxane, anthracycline regimen as the first-line metastatic treatment and enter the trial at confirmed progression (second-line)

• No bone-limited disease

• No disease suitable for endocrine therapy alone

• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified
• Sex: female
• WHO performance status 0-2
• Life expectancy ≥ 3 months
• AST and/or ALT ≤ 5 times upper limit of normal (ULN) (≤ 3 if alkaline phosphatase > 5 times ULN)
• Glomerular filtration rate ≥ 30 mL/min
• Normal urea and creatinine
• Normal hematological and biochemical studies
• Normal bilirubin
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 6 months after completion of study treatment
• Negative pregnancy test
• No known allergy to platinum compounds or mannitol
• No known sensitivity to taxanes
• No other malignancy within the past 10 years except adequately treated in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin
• No sensory or motor neuropathy > grade 1
• No other serious uncontrolled medical conditions or concurrent medical illness that would preclude study compliance
• No contraindication to chemotherapy

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 12 months since prior taxane therapy
• No prior chemotherapy with a platinum drug, unless treatment was for a non-breast cancer-related disease more than 10 years ago