Efficacy Study of Olaparib With Paclitaxel Versus Paclitaxel in Gastric Cancer Patients

• ClinicalTrials.gov Identifier: NCT01063517
• Recruitment Status: Completed
• First Posted: February 5, 2010
• Results First Posted: April 30, 2015
• Last Update Posted: July 20, 2023
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: February 4, 2010
• First Posted Date: February 5, 2010
• Results First Submitted Date: January 13, 2015
• Results First Posted Date: April 30, 2015
• Last Update Posted Date: July 20, 2023
• Actual Study Start Date: February 2, 2010
• Actual Primary Completion Date: May 11, 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 14, 2015)

• Progression Free Survival (PFS) in the Overall Study Population [ Time Frame: Tumour assessments were carried out at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed maximum up to 27 months ]
  PFS is defined as the time from randomisation till objective progression or death. In absence of progression or death, the time is calculated from randomisation till last evaluable scanning visit.
• Progression Free Survival (PFS) in Patients With Tumours Defined as Homologous Recombination Deficient by Loss of Ataxia-Telangiectasia Mutation (ATM) Protein [ATM Negative Patients] [ Time Frame: Tumour assessments are carried out at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed maximum up to 27 months ]
  PFS is defined as the time from randomisation till objective progression or death. In absence of progression or death, the time is calculated from randomisation till last evaluable scanning visit.

Original Primary Outcome Measures (submitted: February 4, 2010)

• Efficacy (PFS) in the overall study population) [ Time Frame: Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1 ]
• Efficacy (PFS) in patients with tumours defined as HRD by loss of ATM protein ("ATM negative patients") [ Time Frame: Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1 ]

Current Secondary Outcome Measures (submitted: April 14, 2015)

• Overall Survival (OS) in the Overall Study Population [ Time Frame: Survival follow up from randomisation till death of the patient or till end of study in absence of death, assessed maximum up to 27 months ]
  Overall survival is defined as the duration from randomisation till death. In absence of death, the time is calculated from randomisation till the date subject last known to be alive.
• Overall Survival (OS) in ATM Negative Patients [ Time Frame: Survival follow up from randomisation till death of the patient or till end of study in absence of death, assessed maximum up to 27 months ]
  Overall survival is defined as the duration from randomisation till death. In absence of death, the time is calculated from randomisation till the date subject last known to be alive.
• Objective Response Rate (ORR) in the Overall Study Population [ Time Frame: Tumour assessments carried out at baseline, 28 days before randomisation then every 8 weeks until week 40, after week 40 assessments will be carried out every 16 weeks until objective disease progression, assessed maximum up to 27 months ]
  Objective response rate is the proportion of patients with at least one measurable lesion at baseline, who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1).
• Objective Response Rate (ORR) in the ATM Negative Patients [ Time Frame: Tumour assessments carried out at baseline, 28 days before randomisation then every 8 weeks until week 40, after week 40 assessments will be carried out every 16 weeks until objective disease progression, assessed maximum up to 27 months ]
  Objective response rate is the proportion of ATM negative patients with at least one measurable lesion at baseline, who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1).
• Percentage Change in Tumour Size at Week 8 in the Overall Study Population [ Time Frame: Tumour scans done at Baseline and week 8 ]
  Percentage change in tumour size from baseline to Week 8 calculated as 100 X (week 8 tumour size - baseline tumour size) / (baseline tumour size)
• Percentage Change in Tumour Size at Week 8 in the ATM Negative Patients [ Time Frame: Tumour scans done at Baseline and week 8 ]
  Percentage change in tumour size from baseline to Week 8 calculated as 100 X (week 8 tumour size - baseline tumour size) / (baseline tumour size)
• Time to Deterioration in Global Quality of Life (QoL) Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ]
  Time calculated from randomisation till worsening of Global QoL score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data
• Time to Deterioration in QoL Fatigue Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ]
  Time calculated from randomisation till worsening of fatigue score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data
• Time to Deterioration in QoL Nausea & Vomiting Domain Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ]
  Time calculated from randomisation till worsening of nausea & vomiting domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data
• Time to Deterioration in QoL Pain Domain Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ]
  Time calculated from randomisation till worsening of pain domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data
• Time to Deterioration in QoL Dysphagia Domain Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ]
  Time calculated from randomisation till worsening of dysphagia domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data
• Time to Deterioration in QoL Eating Restriction Domain Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ]
  Time calculated from randomisation till worsening of eating restriction domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data
• Time to Deterioration in QoL Stomach Pain Domain Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ]
  Time calculated from randomisation till worsening of stomach pain domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data
• Time to Deterioration in QoL Reflux Domain Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ]
  Time calculated from randomisation till worsening of reflux domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data
• Time to Deterioration in QoL Anxiety Domain Score in the Overall Study Population [ Time Frame: Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months ]
  Time calculated from randomisation till worsening of anxiety domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data

Original Secondary Outcome Measures (submitted: February 4, 2010)

• To determine the safety and tolerability of olaparib when given in combination with paclitaxel in patients with recurrent and metastatic gastric cancer who progress following first-line therapy [ Time Frame: Safety, adverse events and, laboratory findings at every visit ]
• Assess the efficacy of olaparib when given in combination with paclitaxel compared to paclitaxel alone as defined by overall survival, response rate and percentage change in tumor size at Wk 8 in all patients with recurrent and metastatic gastric cancer [ Time Frame: % change in tumour size at 8 weeks ]
• To conduct a preliminary assessment of the effects of olaparib when given in combination with paclitaxel on the time to deterioration of disease related symptom and HRQoL as assessed by the EORTC QLQ-C30 + -STO22 questionnaires [ Time Frame: Day 1, Day 29 and then every 4 weeks until discontinuation ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy Study of Olaparib With Paclitaxel Versus Paclitaxel in Gastric Cancer Patients
• Official Title: A Randomised, Double Blinded, Multicentre Phase II Study to Assess the Efficacy of Olaparib (AZD2281, KU-0059436) in Combination With Paclitaxel Versus Paclitaxel in Patients With Recurrent or Metastatic Gastric Cancer Who Progress Following First-line Therapy
• Brief Summary: To assess the efficacy of olaparib when given in combination with paclitaxel compared with paclitaxel alone as defined by progression-free survival (PFS), in all patients with recurrent and metastatic gastric cancer who progress following first-line therapy.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Gastric Cancer

Intervention

• Drug: olaparib
  100mg BID oral tablet continuous
• Drug: paclitaxel
  iv infusion 80mg/m2 on Day 1, 8 and 15 of a 28 day cycle
  Other Name: Taxol
• Drug: Placebo
  100mg BID oral tablet to match olaparib tablet

Study Arms

• Experimental: 1
  Olaparib + paclitaxel
  Interventions:

  • Drug: olaparib
  • Drug: paclitaxel
• Active Comparator: 2
  paclitaxel + placebo
  Interventions:

  • Drug: paclitaxel
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 12, 2017): 124
• Original Estimated Enrollment (submitted: February 4, 2010): 120
• Actual Study Completion Date: June 29, 2023
• Actual Primary Completion Date: May 11, 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Recurrent or metastatic gastric cancer that has progressed following first line-therapy
• Confirmed ATM protein status by IHC archival tumour sample
• At least one lesion (measurable and/or non-measurable) that can be accurately assessed by imaging (CT/MRI) at baseline and follow up visits

Exclusion Criteria:

• More than one prior chemotherapy regimen for the treatment of gastric cancer in the metastatic or recurrent setting
• Any previous treatment with a PARP inhibitor, including olaparib
• Patients with second primary cancer, except; adequately treated non melanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for >5 years

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 130 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Korea, Republic of

Administrative Information

• NCT Number: NCT01063517
• Other Study ID Numbers: D0810C00039
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Current Responsible Party: AstraZeneca
• Original Responsible Party: MSD, AstraZeneca
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Jane Robertson, BSc, MBCHB, MD; AstraZeneca
• Principal Investigator: Yung-Jue Bang, MD; Seoul National University Hospital

• PRS Account: AstraZeneca
• Verification Date: July 2023