Metastatic or recurrent locally advanced disease Cancer Cancer
Conditions
Interventions
Arm A: Carboplatin area under the concentration?time curve (AUC) six, every three weeks for six cycles (18 weeks)
Arm B: Docetaxel 100 mg/m^2, every three weeks for six cycles (18 week
Sponsors
Institute of Cancer Research and King's College London (UK)
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed ER-, PR-, primary breast cancer (Allred less than three or H score less than ten or ER- and PR- negative, if other cut-offs used [e.g., 1%, 5% or 10%]) 2. Histologically confirmed HER2- primary breast cancer (ImmunoHistoChemistry [IHC] scoring 0 or 1+ for HER2 or non-amplified for HER2 [Fluorescence In Situ Hybridisation {FISH}]) 3. Measurable confirmed metastatic or recurrent locally advanced disease unsuitable for local therapy 4. Patients with stable, treated brain metastases will be eligible providing informed consent can be given and that other sites of measurable disease are present 5. Eastern Cooperative Oncology Group (ECOG) performance status zero, one or two 6. Adequate haematology, biochemical indices (Full Blood Count [FBC], Urea and Electrolytes [U & Es]) 7. Liver Function Tests (LFTs): normal bilirubin, Aspartate Aminotransferase (AST) and/or Alanine Aminotransferase (ALT) less than or equal to 3 x Upper Limit of Normal (ULN) if Alkaline Phosphatase is greater than 5 x ULN (or an isolated elevation AST/ALT of less than or equal to 5 x ULN) 8. Adequate renal function 9. Written informed consent, able to comply with treatment and follow-up
Exclusion criteria
Exclusion criteria: 1. Original primary tumour or subsequent relapse known to be positive for any of ER, PR, or HER2 receptors 2. Patients with inoperable locally advanced disease suitable for local radiotherapy or an anthracycline containing regimen 3. Patients unfit for chemotherapy or those with neuropathy greater than grade one (sensory or motor) 4. Known allergy to platinum compounds or to mannitol 5. Known sensitivity to taxanes 6. Previous exposure to a taxane in adjuvant chemotherapy within 12 months of trial entry 7. Previous treatment with a taxane for recurrent/metastatic disease 8. Previous treatment with a platinum chemotherapy drug 9. LFTs: abnormal bilirubin (greater than ULN), AST and/or ALT greater than 3 x ULN and Alkaline Phosphatase greater than 5 x ULN (or an isolated elevation AST/ALT of greater than or equal to 5 x ULN) 10. Patients with a life expectancy of less than three months 11. 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 ten years 12. Patients with bone limited disease 13. Other serious uncontrolled medical conditions or concurrent medical illness likely to compromise life expectancy and/or the completion of trial therapy 14. Pregnant, lactating or potentially childbearing women not using adequate contraception (documentation of a negative serum Human Choronic Gonadotropin [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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response will be evaluated after three and six cycles of chemotherapy using modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, with appropriate clinical assessment and radiological investigations. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Time to progression: this will be defined according to RECIST criteria and will be measured from the start of treatment until the confirmation of progression 2. Progression free survival: this will be defined according to RECIST criteria and will be measured from the start of treatment until the confirmation of progression or death. Response to second line therapy on progression will be assessed using RECIST criteria as described for the primary endpoint 3. Time to treatment failure: this will be defined as time from randomisation to discontinuation of protocol treatment for any reason, or progression of disease as defined by RECIST 4. Overall survival: this will be defined as time from randomisation until death from any cause in the intention to treat population 5. Toxicity will be assessed throughout the treatment period using the National Cancer Institute Common Terminology Criteria for Adverse Events version three (NCI CTCAE v3.0). | — |
Countries
United Kingdom
Outcome results
None listed