Saracatinib and Paclitaxel in Platinum-resistant Ovarian Cancer (SaPPrOC)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Cancer |
Drug: Paclitaxel Drug: Saracatinib Drug: Matched placebo |
Phase 2 Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| Official Title: | A Randomised Placebo-controlled Trial of Saracatinib (AZD0530) Plus Weekly Paclitaxel in Platinum Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer |
- 6 month progression-free survival rate (based on combined RECIST v1.1/GCIG CA125 criteria) [ Time Frame: 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. ] [ Designated as safety issue: No ]
Where a patient's disease is not measurable by RECIST v1.1, response may be based on GCIG CA125 criteria alone.
The 6 month progression-free survival rate will be calculated by the trial statistician during the final analysis.
- Overall survival rate at 2 years [ Time Frame: 2 years after end of trial ] [ Designated as safety issue: No ]
- Objective Response Rate based on Investigator assessment based on RECIST v1.1 and GCIG CA125 criteria [ Time Frame: 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. ] [ Designated as safety issue: No ]
Where a patient's disease is not measurable by RECIST v1.1, response may be based on GCIG CA125 criteria alone.
Objective Response Rate will be calculated by the trial statistician during the final analysis.
- Duration of Response [ Time Frame: 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. ] [ Designated as safety issue: Yes ]
Where a patient's disease is not measurable by RECIST v1.1, response may be based on GCIG CA125 criteria alone.
Duration of Response will be calculated by the trial statistician during the final analysis.
- Health Economics and Quality of Life Outcomes based on FACT-O and EQ-5D [ Time Frame: Patients will fill in FACT-O and EQ-5D questionnaires at the following timepoints: baseline; Weeks 1, 3 and 6 of every chemotherapy cycle; at every follow up visit ] [ Designated as safety issue: No ]
- Safety and tolerability (Toxicity) [ Time Frame: To be assessed at every timepoint i.e. baseline; Weeks 1-8 of each chemotherapy cycle; at every follow up visit ] [ Designated as safety issue: Yes ]
- Progression-free survival as a Time to Event endpoint based on RECIST 1.1 and GCIG CA125 criteria [ Time Frame: 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. ] [ Designated as safety issue: No ]
Where a patient's disease is not measurable by RECIST v1.1, response may be based on GCIG CA125 criteria alone.
Progression-free survival as a Time to Event endpoint will be calculated by the trial statistician during the final analysis.
- Time To Progression based on RECIST v1.1 and GCIG CA125 criteria [ Time Frame: 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. ] [ Designated as safety issue: No ]
Where a patient's disease is not measurable by RECIST v1.1, response may be based on GCIG CA125 criteria alone.
Time To Progression will be calculated by the trial statistician during the final analysis.
| Estimated Enrollment: | 102 |
| Study Start Date: | April 2011 |
| Estimated Study Completion Date: | March 2013 |
| Primary Completion Date: | November 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Active Comparator: Saracatinib plus weekly paclitaxel |
Drug: Paclitaxel
Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles 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.
Drug: Saracatinib
Saracatinib 175 mg PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression
|
| Placebo Comparator: Placebo plus weekly paclitaxel |
Drug: Paclitaxel
Paclitaxel 80 mg/m2 weekly for 6 weeks followed by a 2 week break (1 cycle), for 4 cycles initially (32 weeks). If there is evidence of on-going response after 4 cycles, 3 further cycles 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.
Drug: Matched placebo
Matched placebo PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression
|
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 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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Inclusion criteria:
- Confirmed relapsed ovarian, fallopian tube or primary peritoneal cancer AND relapse within the platinum-resistant (progression must not be based on CA125 alone) time-frame, i.e. have progressed within 6 months of platinum therapy.
- Patients need not have received prior taxane; if patients have received prior taxane, the interval since treatment must be known. Patients will be stratified as <6 months or 6+ months taxane interval/no prior taxane.
- Patients will generally have received at least 2 lines of prior chemotherapy, but may enter if they have relapsed within 6 months of first line therapy. Patients may have received prior liposomal doxorubicin, although this is NOT a requirement. The treatment immediately prior to study entry need not be platinum-based.
- Measurable or evaluable disease (if not measurable by RECIST v1.1 criteria, patients must be evaluable by GCIG CA125 criteria).
- ECOG PS 0-2
- Adequate haematological and biochemical function.
Exclusion criteria
- Prior administration of weekly paclitaxel.
- Tumours of malignant mixed mesodermal (MMMT) or mucinous subtypes, or non-epithelial ovarian cancers (e.g. Brenner tumours, Sex-cord tumours).
- Unresolved bowel obstruction.
- Chemotherapy within the preceding 3 weeks.
- Radiotherapy within the preceding 3 weeks.
- Treatment with any investigational agent within the preceding 4 weeks or within 5 half-lives of the investigational agent, whichever is longer.
- Known leptomeningeal involvement or intracranial disease.
- Evidence of interstitial lung disease (bilateral, diffuse, parenchymal lung disease).
- Resting ECG with measurable QTc interval of >480 msec at 2 or more time points within a 24 hour period.
- Pregnant or lactating females.
- Fertile women of childbearing potential not willing to use highly effective contraception for the duration of trial treatment and for at least 6 months after the last administration of saracatinib +/- paclitaxel.
- Inability or unwillingness to give informed consent.
- Ongoing active infection or a documented history of HIV infection, Hepatitis B or C.
- Concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/IV cardiac disease.
- Concurrent autoimmune disorder, e.g. systemic lupus or any demyelinating disease.
- Use of immunosuppressive therapy or corticosteroids taken within the 4 weeks prior to study entry and during the treatment period.
Contacts and Locations| United Kingdom | |
| Addenbrooke's Hospital | |
| Cambridge, Cambridgeshire, United Kingdom, BC2 0QQ | |
| The Royal Mardsen Hospital | |
| London, Greater London, United Kingdom, SW3 6JJ | |
| St Bartholomew's Hospital | |
| London, Greater London, United Kingdom, EC1A 7BE | |
| University College London Hospital | |
| London, Greater London, United Kingdom, NW1 2PG | |
| Guy's Hospital | |
| London, Greater London, United Kingdom, SE1 9RT | |
| The Christie NHS Foundation Trust | |
| Manchester, Greater Manchester, United Kingdom, M20 4BX | |
| Mount Vernon Hospital | |
| Rickmansworth, Middlesex, United Kingdom, HA6 2RN | |
| The Churchill Hospital | |
| Oxford, Oxfordshire, United Kingdom, OX3 7LJ | |
| Queen's Hospital | |
| Burton upon Trent, Staffordshire, United Kingdom, DE13 0RB | |
| Royal Marsden Hospital | |
| Sutton, Surrey, United Kingdom, SM2 5PT | |
| St James's University Hospital | |
| Leeds, Yorkshire, United Kingdom, LS9 7TF | |
| Beatson West of Scotland Cancer Centre | |
| Glasgow, United Kingdom, G12 0YN | |
| Principal Investigator: | Iain McNeish | Barts and the London NHS Trust |
More Information
No publications provided
| Responsible Party: | University College, London |
| ClinicalTrials.gov Identifier: | NCT01196741 History of Changes |
| Other Study ID Numbers: | UCL/09/105, Funder reference (academic), Funder reference (industry), 2009-017171-13 |
| Study First Received: | September 1, 2010 |
| Last Updated: | February 18, 2013 |
| Health Authority: | United Kingdom: Medicines and Healthcare products Regulatory Agency (executive agency of the UK Department of Health) |
Additional relevant MeSH terms:
|
Ovarian Neoplasms Peritoneal Neoplasms Fallopian Tube Neoplasms Endocrine Gland Neoplasms Neoplasms by Site Neoplasms Ovarian Diseases Adnexal Diseases Genital Diseases, Female Genital Neoplasms, Female Urogenital Neoplasms Endocrine System Diseases Gonadal Disorders Abdominal Neoplasms |
Digestive System Neoplasms Digestive System Diseases Peritoneal Diseases Fallopian Tube Diseases Paclitaxel Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents, Phytogenic Antineoplastic Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 23, 2013