E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic breast cancer in women with BRCA1 or BRCA 2 mutation |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess whether chemotherapy with carboplatin is a safe and effective treatment for women with metastatic breast cancer who are BRCA 1 or BRCA 2 carriers. The response to treatment with carboplatin will be compared to the reponse to the current standard treatment, docetaxel. |
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E.2.2 | Secondary objectives of the trial |
To determine whether treatment with carboplatin prolongs the time to progression of metastatic breast cancer in women who are BRCA 1 or BRCA 2 carriers. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
·Histologically confirmed measurable metastatic breast cancer in known BRCA1 or 2 mutation carriers, where chemotherapy is the treatment of choice ·Patients with stable, treated brain metastases will be eligible providing informed consent can be given and that other sites of measurable disease are present ·Patients with bone metastases currently receiving bisphosphonates for palliation will be eligible providing other sites of measurable disease are present ·WHO Performance Status 0, 1 or 2 ·Normal haematology, biochemical indices (FBC, U & E’s) ·LFT’s = Normal bilirubin, AST and/or ALT <or=3 x ULN and Alk Phos <or=5 x ULN (n.b. Alk Phos <or=2.5 x ULN if AST and/or ALT >or=1.5 x ULN) ·Normal renal function ·Written informed consent and able to comply with treatment and willing to attend long term follow-up
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E.4 | Principal exclusion criteria |
·Patients unfit for chemotherapy or those with neuropathy >grade 1 (sensory or motor) ·Known allergy to platinum compounds or to mannitol ·Previous treatment with a platinum chemotherapy drug ·LFT’s = Abnormal bilirubin (> ULN), AST and/or ALT >3 x ULN and Alk Phos >5 x ULN (n.b. Alk Phos >2.5 x ULN if AST and/or ALT >1.5 x ULN) ·Patients with a life expectancy of less than 3 months ·Previous malignancies other than adequately treated in situ carcinoma of the uterine cervix or basal or squamous cell carcinoma of the skin, unless there has been a disease free interval of at least 10 years ·Patients with bone limited disease or suitable for endocrine therapy alone ·Other serious uncontrolled medical conditions or concurrent medical illness likely to compromise life expectancy and/or the completion of trial therapy ·Pregnant, lactating or potentially childbearing women not using adequate contraception (documentation of a negative serum HCG pregnancy test should be available for pre-menopausal women with intact reproductive organs, or women less than two years after the menopause. Fertile women and their partners must use a medically acceptable contraceptive throughout the treatment period and for six months following cessation of treatment. Subjects must be made aware before entering the trial of the risk in becoming pregnant). n.b. Prior exposure to taxanes does not exclude patients providing that there is >or=12 months between previous exposure and trial entry.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary: Response and toxicity Response will be evaluated after 3 and 6 cycles of chemotherapy using RECIST criteria, with appropriate clinical assessment and radiological investigations. There will be a ‘response evaluation committee’ to independently assess response. Toxicity will be assessed throughout the treatment period using the NCI CTCAE v3.0 12/12/03
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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This is a two-stage trial. The first stage will cover the randomisation, treatment and first assessment of the patients. The end of the first stage is defined as one month from the date when the last patient has completed trial therapy. Stage two, the non-interventional follow up period of the trial, will then commence. All patients will be followed for life. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 10 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 10 |
E.8.9.2 | In all countries concerned by the trial months | 0 |