Saracatinib and Paclitaxel in Platinum-resistant Ovarian Cancer
- Conditions
- Ovarian CancerFallopian Tube CancerPrimary Peritoneal Cancer
- Interventions
- Registration Number
- NCT01196741
- Lead Sponsor
- University College, London
- Brief Summary
The purpose of this study is to investigate whether the addition of the Src inhibitor saracatinib (AZD0530) to weekly paclitaxel improves efficacy, compared with paclitaxel plus placebo, in patients with relapsed platinum-resistant ovarian cancer. The trial will also determine toxicity and ascertain whether the combination of paclitaxel plus saracatinib should proceed to a phase III trial.
- Detailed Description
A multicentre, randomised, double-blind, placebo-controlled Phase II trial will be conducted. The overall aim of the trial is to investigate whether the addition of saracatinib to weekly paclitaxel improves efficacy, as measured by progression free survival, compared with paclitaxel plus placebo. The trial will also determine toxicity and ascertain whether the combination of paclitaxel plus saracatinib should proceed to a phase III trial.
The toxicity data from Study NCT00610714 (D8180C00015) suggests that a small number of patients could experience febrile neutropaenia during their first chemotherapy cycle. To combat this, saracatinib (175 mg OD)/matched placebo will begin 1 week prior to commencement of chemotherapy, and be given continuously until progression.
All patients will receive cycles of weekly paclitaxel chemotherapy. One cycle will consist of weekly paclitaxel (80 mg/m2) for 6 weeks followed by 2 weeks rest. If there is evidence of on-going response after 4 cycles, 3 further cycles of saracatinib/placebo plus weekly paclitaxel will be given, unless there is dose-limiting toxicity or the patient requests to discontinue treatment. If best response is stable disease after 4 cycles, treatment should be discontinued but may continue at the discretion of the Investigator.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 107
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Saracatinib plus weekly paclitaxel Saracatinib - Placebo plus weekly paclitaxel Matched placebo - Saracatinib plus weekly paclitaxel Paclitaxel - Placebo plus weekly paclitaxel Paclitaxel -
- Primary Outcome Measures
Name Time Method 6 Month Progression-free Survival Rate (PFS) (Based on Combined Response Evaluation Criteria In Solid Tumours (RECIST) v1.1 +/- Gynecologic Cancer Intergroup (GCIG) CA125 Criteria) Using RECIST v1.1 at baseline; at Week 7 or 8 of each chemotherapy cycle; and 3 monthly during follow up. CA125 response will be assessed at baseline, weeks 1, 3 and 6 of each chemotherapy cycle, and at every follow up visit. Where a patient's disease is not measurable by RECIST v1.1, response may be based on GCIG CA125 criteria plus symptoms.
The 6 month progression-free survival rate will be calculated by the trial statistician during the final analysis.
- Secondary Outcome Measures
Name Time Method Median Duration of Response Using RECIST v1.1 at baseline; at Week 7 or 8 of each chemotherapy cycle; and 3 monthly during follow up. CA125 response will be assessed at baseline, weeks 1, 3 and 6 of each chemotherapy cycle, and at every follow up visit. Where a patient's disease is not measurable by RECIST v1.1, response may be based on GCIG CA125 criteria plus symptoms.
Duration of Response will be calculated by the trial statistician during the final analysis.Median Time To Progression Based on RECIST v1.1 and GCIG CA125 Criteria Using RECIST v1.1 at baseline; at Week 7 or 8 of each chemotherapy cycle; and 3 monthly during follow up. CA125 response will be assessed at baseline, weeks 1, 3 and 6 of each chemotherapy cycle, and at every follow up visit. Where a patient's disease is not measurable by RECIST v1.1, response may be based on GCIG CA125 criteria plus symptoms.
Time To Progression will be calculated by the trial statistician during the final analysis.Overall Survival First saracatinib/placebo dose until death, assessed up to 36 months Objective Response Rate Based on Investigator Assessment Based on RECIST v1.1 +/- GCIG CA125 Criteria Using RECIST v1.1 at baseline; at Week 7 or 8 of each chemotherapy cycle; and 3 monthly during follow up. CA125 response will be assessed at baseline, weeks 1, 3 and 6 of each chemotherapy cycle, and at every follow up visit. Where a patient's disease is not measurable by RECIST v1.1, response may be based on GCIG CA125 criteria plus symptoms.
Quality of Life: Trial Outcome Index (TOI) Based on FACT-O Patients will fill in FACT-O questionnaires at the following timepoints: baseline; Weeks 1, 3 and 6 of every chemotherapy cycle; at every follow up visit The TOI value for each patient is derived at each timepoint by calculating the sum of 3 subscales: Physical Well-Being (PWB), Functional Well-Being (FWB), Additional Concerns. Each subscale score is derived from questions with 4 answers (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). In each subscale reversals are performed and the individual question scores added together. This value is then multiplied by the number of questions within the subscale, and divided by the number of questions answered to derive a subscale score. The higher each subscale score, the better the QoL.
PWB 7 questions, lower values=better QoL.
FWB 7 questions, higher values=better QoL.
Additional concerns 11 questions (higher values in 6 questions=better QoL; higher values in 5 questions=worse QoL)
The TOI is reported for each arm based on the average TOI score of each patient calculated across the outcome measure time frame. The higher the TOI, the better the QoL.Median PFS From first saracatinib/placebo dose to first documented progression and/or death, assessed up to 36 months
Trial Locations
- Locations (12)
St Bartholomew's Hospital
🇬🇧London, Greater London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, Greater Manchester, United Kingdom
University College London Hospital
🇬🇧London, Greater London, United Kingdom
The Royal Mardsen Hospital
🇬🇧London, Greater London, United Kingdom
Mount Vernon Hospital
🇬🇧Rickmansworth, Middlesex, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
St James's University Hospital
🇬🇧Leeds, Yorkshire, United Kingdom
Royal Marsden Hospital
🇬🇧Sutton, Surrey, United Kingdom
The Churchill Hospital
🇬🇧Oxford, Oxfordshire, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Queen's Hospital
🇬🇧Burton upon Trent, Staffordshire, United Kingdom
Guy's Hospital
🇬🇧London, Greater London, United Kingdom