Saracatinib and Paclitaxel in Platinum-resistant Ovarian Cancer
SaPPrOC
A Randomised Placebo-controlled Trial of Saracatinib (AZD0530) Plus Weekly Paclitaxel in Platinum Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer
4 other identifiers
interventional
107
1 country
12
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 ovarian-cancer
Started Mar 2011
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 1, 2010
CompletedFirst Posted
Study publicly available on registry
September 8, 2010
CompletedStudy Start
First participant enrolled
March 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2014
CompletedResults Posted
Study results publicly available
May 5, 2015
CompletedMay 5, 2015
January 1, 2014
1.7 years
September 1, 2010
September 18, 2014
April 17, 2015
Conditions
Outcome Measures
Primary Outcomes (1)
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)
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.
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.
Secondary Outcomes (6)
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.
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.
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
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.
- +1 more secondary outcomes
Study Arms (2)
Saracatinib plus weekly paclitaxel
ACTIVE COMPARATORPlacebo plus weekly paclitaxel
PLACEBO COMPARATORInterventions
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.
Saracatinib 175 mg PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression
Matched placebo PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression
Eligibility Criteria
You may qualify if:
- Confirmed relapsed ovarian, fallopian tube or primary peritoneal cancer AND relapse within the platinum-resistant (progression must not be based on Cancer Antigen 125 (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 Response Evaluation Criteria In Solid Tumours (RECIST) v1.1 criteria, patients must be evaluable by Gynecologic Cancer InterGroup (GCIG) CA125 criteria).
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2
- Adequate haematological and biochemical function.
You may not qualify if:
- 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.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University College, Londonlead
- AstraZenecacollaborator
- Cancer Research UKcollaborator
Study Sites (12)
Addenbrooke's Hospital
Cambridge, Cambridgeshire, BC2 0QQ, United Kingdom
St Bartholomew's Hospital
London, Greater London, EC1A 7BE, United Kingdom
University College London Hospital
London, Greater London, NW1 2PG, United Kingdom
Guy's Hospital
London, Greater London, SE1 9RT, United Kingdom
The Royal Mardsen Hospital
London, Greater London, SW3 6JJ, United Kingdom
The Christie NHS Foundation Trust
Manchester, Greater Manchester, M20 4BX, United Kingdom
Mount Vernon Hospital
Rickmansworth, Middlesex, HA6 2RN, United Kingdom
The Churchill Hospital
Oxford, Oxfordshire, OX3 7LJ, United Kingdom
Queen's Hospital
Burton-on-Trent, Staffordshire, DE13 0RB, United Kingdom
Royal Marsden Hospital
Sutton, Surrey, SM2 5PT, United Kingdom
St James's University Hospital
Leeds, Yorkshire, LS9 7TF, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN, United Kingdom
Related Publications (1)
McNeish IA, Ledermann JA, Webber L, James L, Kaye SB, Hall M, Hall G, Clamp A, Earl H, Banerjee S, Kristeleit R, Raja F, Feeney A, Lawrence C, Dawson-Athey L, Persic M, Khan I. A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancerdagger. Ann Oncol. 2014 Oct;25(10):1988-1995. doi: 10.1093/annonc/mdu363. Epub 2014 Jul 28.
PMID: 25070546DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Prof Iain McNeish, Professor of Gynaecological Oncology
- Organization
- University of Glasgow
Study Officials
- PRINCIPAL INVESTIGATOR
Iain McNeish
Barts and the London NHS Trust
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 1, 2010
First Posted
September 8, 2010
Study Start
March 1, 2011
Primary Completion
November 1, 2012
Study Completion
January 1, 2014
Last Updated
May 5, 2015
Results First Posted
May 5, 2015
Record last verified: 2014-01