Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer

Sponsor

University College London Hospitals (Other)

Overall Status

Completed

CT.gov ID

NCT00321633

Collaborator

(none)

148

Enrollment

Locations

5.9

Patients Per Site

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
brca1 Mutation Carrier brca2 Mutation Carrier Breast Cancer Hereditary Breast/Ovarian Cancer (brca1, brca2)	Drug: carboplatin Drug: docetaxel	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

148 participants

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2005

Actual Primary Completion Date :

Sep 1, 2009

Outcome Measures

Primary Outcome Measures

Response and toxicity []

Secondary Outcome Measures

Time to progression []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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