A Randomised Placebo-controlled Trial of Saracatinib (AZD0530) Plus Weekly Paclitaxel in Platinum Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer
18 Years
N/A
Female
Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer
Trial Information
A Randomised Placebo-controlled Trial of Saracatinib (AZD0530) Plus Weekly Paclitaxel in Platinum Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer
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.
Inclusion Criteria
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.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Outcome Measure:
6 month progression-free survival rate (based on combined RECIST v1.1/GCIG CA125 criteria)
Outcome Description:
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.
Outcome 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.
Safety Issue:
No
Principal Investigator
Iain McNeish
Investigator Role:
Principal Investigator
Investigator Affiliation:
Barts and the London NHS Trust
Authority:
United Kingdom: Medicines and Healthcare products Regulatory Agency (executive agency of the UK Department of Health)
Study ID:
UCL/09/105
NCT ID:
NCT01196741
Start Date:
April 2011
Completion Date:
March 2013
Related Keywords:
- Ovarian Cancer
- Fallopian Tube Cancer
- Primary Peritoneal Cancer
- Ovarian Neoplasms
- Peritoneal Neoplasms
- Fallopian Tube Neoplasms
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