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

Primary Purpose

Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer

Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Paclitaxel
Saracatinib
Matched placebo
Sponsored by
University College, London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion criteria:

  • 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.

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.

Sites / Locations

  • Addenbrooke's Hospital
  • St Bartholomew's Hospital
  • University College London Hospital
  • Guy's Hospital
  • The Royal Mardsen Hospital
  • The Christie NHS Foundation Trust
  • Mount Vernon Hospital
  • The Churchill Hospital
  • Queen's Hospital
  • Royal Marsden Hospital
  • St James's University Hospital
  • Beatson West of Scotland Cancer Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Saracatinib plus weekly paclitaxel

Placebo plus weekly paclitaxel

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall Survival
Objective Response Rate Based on Investigator Assessment Based on RECIST v1.1 +/- 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.
Median Duration of Response
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.
Quality of Life: Trial Outcome Index (TOI) Based on FACT-O
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 Time To Progression Based on RECIST v1.1 and 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. Time To Progression will be calculated by the trial statistician during the final analysis.
Median PFS

Full Information

First Posted
September 1, 2010
Last Updated
April 17, 2015
Sponsor
University College, London
Collaborators
AstraZeneca, Cancer Research UK
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1. Study Identification

Unique Protocol Identification Number
NCT01196741
Brief Title
Saracatinib and Paclitaxel in Platinum-resistant Ovarian Cancer
Acronym
SaPPrOC
Official Title
A Randomised Placebo-controlled Trial of Saracatinib (AZD0530) Plus Weekly Paclitaxel in Platinum Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London
Collaborators
AstraZeneca, Cancer Research UK

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
107 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Saracatinib plus weekly paclitaxel
Arm Type
Active Comparator
Arm Title
Placebo plus weekly paclitaxel
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Saracatinib
Intervention Description
Saracatinib 175 mg PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression
Intervention Type
Drug
Intervention Name(s)
Matched placebo
Intervention Description
Matched placebo PO once daily, to begin 1 week prior to commencement of chemotherapy, taken continuously until progression
Primary Outcome Measure Information:
Title
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)
Description
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.
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.
Secondary Outcome Measure Information:
Title
Overall Survival
Time Frame
First saracatinib/placebo dose until death, assessed up to 36 months
Title
Objective Response Rate Based on Investigator Assessment Based on RECIST v1.1 +/- GCIG CA125 Criteria
Description
Where a patient's disease is not measurable by RECIST v1.1, response may be based on GCIG CA125 criteria plus symptoms.
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.
Title
Median Duration of Response
Description
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.
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.
Title
Quality of Life: Trial Outcome Index (TOI) Based on FACT-O
Description
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.
Time Frame
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
Title
Median Time To Progression Based on RECIST v1.1 and GCIG CA125 Criteria
Description
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.
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.
Title
Median PFS
Time Frame
From first saracatinib/placebo dose to first documented progression and/or death, assessed up to 36 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: 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. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Iain McNeish
Organizational Affiliation
Barts and the London NHS Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Addenbrooke's Hospital
City
Cambridge
State/Province
Cambridgeshire
ZIP/Postal Code
BC2 0QQ
Country
United Kingdom
Facility Name
St Bartholomew's Hospital
City
London
State/Province
Greater London
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
Facility Name
University College London Hospital
City
London
State/Province
Greater London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Facility Name
Guy's Hospital
City
London
State/Province
Greater London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
The Royal Mardsen Hospital
City
London
State/Province
Greater London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Facility Name
The Christie NHS Foundation Trust
City
Manchester
State/Province
Greater Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Mount Vernon Hospital
City
Rickmansworth
State/Province
Middlesex
ZIP/Postal Code
HA6 2RN
Country
United Kingdom
Facility Name
The Churchill Hospital
City
Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OX3 7LJ
Country
United Kingdom
Facility Name
Queen's Hospital
City
Burton upon Trent
State/Province
Staffordshire
ZIP/Postal Code
DE13 0RB
Country
United Kingdom
Facility Name
Royal Marsden Hospital
City
Sutton
State/Province
Surrey
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Facility Name
St James's University Hospital
City
Leeds
State/Province
Yorkshire
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Beatson West of Scotland Cancer Centre
City
Glasgow
ZIP/Postal Code
G12 0YN
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
25070546
Citation
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.
Results Reference
derived

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Saracatinib and Paclitaxel in Platinum-resistant Ovarian Cancer

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