Metastatic breast cancer MedDRA version: 17.0 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
University Hospitals Bristol NHS Foundation trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Written informed consent Metastatic breast cancer, fit to receive cytotoxic chemotherapy as palliative treatment. Measurable disease as per RECIST 1.1 by CT or MRI within 4 weeks of registration. ECOG performance status 0 or 1 No prior cytotoxic chemotherapy for metastatic disease. Neoadjuvant or adjuvant chemotherapy permitted if given more than 3 months prior to registration. Patients may be taxane naive or have received docetaxel chemotherapy in the adjuvant setting. Prior histology to confirm HER 2 negative defined as IHC 0+, 1+ or IHC 2+ with FISH/SISH/CISH (Ratio 6 months. Adequate liver, renal and bone marrow function defined as: Haemoglobin >9.0g/dL Absolute neutrophil count > 1.5 x 10^9/L Platelet count >100 x 10^9/L ALT=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: HER 2 + breast cancer (IHC 3+ or FISH/SISH/CISH ratio 2.0 ) Previous paclitaxel chemotherapy in the adjuvant setting. Prior cytotoxic chemotherapy for metastatic disease. Palliative radio therapy for metastatic disease within 4 weeks of randomisation. Symptomatic brain metastases. History or other malignancy (excluding non-melanomatous skin cancer). Grade = 2 peripheral motor +/or sensory neuropathy. Grade = 2 oral mucositis. History of severe hypersensitivity reaction (= grade 3) to taxanes. History of severe hypersensitivity reaction (= grade 3) to polysorbate 80- containing drugs. Clinically significant (active) cardiovascular disease, including cerebrovascular accident (within 6 months before enrolment), myocardial infarction, arterial thrombotic events within 6 months before enrolment, unstable angina pectoris, New York heart association grade 2 congestive heart failure, serious cardiac arrythmia requiring medication during the study and that might intefere with regularity of the study treatment, or not controlled by medication. Any severe acute or chronic medical condition which could impair the ability of the patient to participate in the study or comply with the study procedures or interfere with interpretation of study results.( such as significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures.) Active infection requiring systemic antibiotics or antifungal medication. Prior endocrine therapy treatment must be stopped before study entry. Concurrent treatment on another clinical trial. Requirement for radiation therapy concurrent withthe study. Inability and unwillingness to comply with study visits, treatment, testing and to comply with the protocol. Other concurrent serious illness or medical conditions which make it undesirable for the patient to enter the trial including uncontrolled diabetes mellitus. Inadequate organ and bone marrow function as evidenced by : Haemoglobin 2.5 x ULN Total bilirubin > 1.5 x ULN Serum creatinine > 1.5 x ULN. If creatinine is 1.0-1.5 x ULN, creatinine clearnace will be calculated according to CKD-EPI formula and patients with creatinine clearance <60mls/min should be excluded. (See appendix 2 for formula) Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5. ( A one week washout period is necessary for patients who are already on these treatments. (Appendix 4) Participation in another clinical trial with any investigational drug within 30 days prior to randomisation. Pregnancy or breast feeding women. Patients with child bearing potential who do not agree to use accepted and effective method of contraception ( barrier method, intrauterine devices, sterilisation) during the study treatment period and for a period of 12 months after the last study drug administration.. Contraindications to the use of corticosteroid treatment. Grade = 2 peripheral neuropathy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assessment in the difference of progression free survival between the 2 groups defined as either the development of disease profgression or death from any cause.;Secondary Objective: To determine the best response rate in each group recorded from the start of treatment to the completion of 6 cycles of treatment. The time to response in each group taken from the time of registration to the CT scan showing a partial response. Overall survival To evaluate the safety and tolerability by assessing the occurence of grade 3 or greater toxicities between the start of treatment and disease progression and the number of serious adverse events. To assess the quality of life using EQ-5D and FACT -B questionnaires. The time to the next cytotoxic chemotherapy treatment.;Primary end point(s): Progression free survival between the two groups from randomisation to either death or disease progression.;Timepoint(s) of evaluation of this end point: Primary efficacy endpoint is the PFS, defined as the time interval between the date of randomisation and the date of tumour progression (defined according to RECIST version 1.1) or death from any cause, whichever comes first. In the absence of confirmation of disease progression or death, PFS time will be censored at the earlier between the date of last valid tumour assessment without evidence of tumour progression and the cut-off date. PFS for patients who have no tumour assessments after baseline and do not die will be censored on the day of randomisation (Day 1). PFS will be compared between the two treatments by the log-rank test procedure stratified by previous chemotherapy in adjuvant setting (docetaxel vs No docetaxel) and subtype tumour (ER positive or negative) as specified at the | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Response Rates Tolerability and Safety Overall Survival Quality of Life;Timepoint(s) of evaluation of this end point: Secondary endpoints analysis Response rates will be estimated as the number of patients with clinical benefit rate (CR + PR + SD) and objective response (CR+PR) recorded from the start of treatment to the completion of 6 cycles of treatment. Overall Survival will be defined as the time period between randomisation and death and will be analysed after the end of the study by referring to data from the hospital statistics. Quality of Life : FACT-B and EQ-5D scores will be presented by treatment group at baseline, prior to cycles 3 and 5 and at the end of treatment visit. | — |
Countries
Ireland, United Kingdom
Contacts
Public ContactSylvia Pearson
University Hospitals Bristol NHS Foundation trust
Outcome results
None listed