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Saracatinib and Paclitaxel in Platinum-resistant Ovarian Cancer (SaPPrOC)

This study has been completed.
Sponsor:
Collaborators:
AstraZeneca
Cancer Research UK
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01196741
First received: September 1, 2010
Last updated: January 22, 2014
Last verified: January 2014
  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

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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.



Enrollment: 107
Study Start Date: March 2011
Study Completion Date: January 2014
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
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01196741

Locations
United Kingdom
Addenbrooke's Hospital
Cambridge, Cambridgeshire, United Kingdom, BC2 0QQ
University College London Hospital
London, Greater London, United Kingdom, NW1 2PG
St Bartholomew's Hospital
London, Greater London, United Kingdom, EC1A 7BE
The Royal Mardsen Hospital
London, Greater London, United Kingdom, SW3 6JJ
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
Sponsors and Collaborators
University College, London
AstraZeneca
Cancer Research UK
Investigators
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: January 22, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Ovarian Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Peritoneal Diseases
Urogenital Neoplasms
Paclitaxel
Saracatinib
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 25, 2014