Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer

A Randomized Phase II Pilot Trial of Carboplatin Compared to Docetaxel for Patients With Metastatic Genetic Breast Cancer [BRCA Trial]

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Hereditary Breast/Ovarian Cancer (brca1, brca2); brca1 Mutation Carrier; brca2 Mutation Carrier
• Intervention / Treatment: Drug: carboplatin; Drug: docetaxel

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 148
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Israel
  • Beer-Sheva, Israel, 84101
    • Soroka University Medical Center
  • Naharia, Israel
    • Naharia Hospital
  • Tel Hashomer, Israel, 52621
    • Chaim Sheba Medical Center
• Portugal
  • Lisbon, Portugal, 1099-023 Codex
    • Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, SA
• Spain
  • Barcelona, Spain, 08035
    • Vall d'Hebrón University Hospital
• Sweden
  • Lund, Sweden, SE-22185
    • Lund University Hospital
• United Kingdom
  • England
    • Cambridge, England, United Kingdom, CB2 2QQ
      • Addenbrooke's Hospital
    • Exeter, England, United Kingdom, EX2 5DW
      • Royal Devon and Exeter Hospital
    • Hampstead, London, England, United Kingdom, NW3 2QG
      • UCL Cancer Institute
    • Leeds, England, United Kingdom, LS9 7TF
      • Leeds Cancer Centre at St. James's University Hospital
    • Leeds, England, United Kingdom, LS16 6QB
      • Cookridge Hospital
    • London, England, United Kingdom, SE1 9RT
      • Guy's Hospital
    • London, England, United Kingdom, SW3 6JJ
      • Royal Marsden - Surrey
    • Manchester, England, United Kingdom, M20 4BX
      • Christie Hospital
    • Merseyside, England, United Kingdom, CH63 4JY
      • Clatterbridge Centre for Oncology
    • Norfolk, England, United Kingdom, NR31 6LA
      • James Paget Hospital
    • Northwood, England, United Kingdom, HA6 2RN
      • Mount Vernon Cancer Centre at Mount Vernon Hospital
    • Norwich, England, United Kingdom, NR4 7UY
      • Norfolk and Norwich University Hospital
    • Poole Dorset, England, United Kingdom, BH15 2JB
      • Dorset Cancer Centre
    • Portsmouth Hants, England, United Kingdom, PO3 6AD
      • Portsmouth Oncology Centre at Saint Mary's Hospital
    • Southampton, England, United Kingdom, SO16 6YD
      • Southampton General Hospital
    • Torquay, England, United Kingdom, TQ2 7AA
      • Torbay Hospital
  • Scotland
    • Edinburgh, Scotland, United Kingdom, EH4 2XU
      • Edinburgh Cancer Centre at Western General Hospital
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 2TL
      • Velindre Cancer Center at Velindre Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Response and toxicity

Secondary Outcome Measures

Outcome Measure
Time to progression

Collaborators and Investigators

• Sponsor: University College London Hospitals
• Investigators: Study Chair: Andrew Tutt, MD, PhD, FRCR, MBBS, MRCP, Guy's Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: May 2, 2006
• First Submitted That Met QC Criteria: May 2, 2006
• First Posted (Estimate): May 4, 2006

Study Record Updates

• Last Update Posted (Estimate): August 26, 2013
• Last Update Submitted That Met QC Criteria: August 23, 2013
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer; hereditary breast/ovarian cancer (BRCA1, BRCA2); BRCA2 mutation carrier; BRCA1 mutation carrier
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Breast Diseases; Breast Neoplasms; Ovarian Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Carboplatin
• Other Study ID Numbers: CDR0000467994; CRUK-BRCA-TRIAL; EUDRACT-2004-001496-20; EU-20603; ISRCTN43372330; BBC-CRUK-BRCA-TRIAL