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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: olaparib
* Drug: paclitaxel
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Olaparib + paclitaxel | Drug: olaparib<br>* 100mg BID oral tablet continuous<br>Drug: paclitaxel<br>* iv infusion 80mg/m2 on Day 1, 8 and 15 of a 28 day cycle<br>* Other names: Taxol;|
| Active Comparator: 2<br>paclitaxel + placebo | Drug: paclitaxel<br>* iv infusion 80mg/m2 on Day 1, 8 and 15 of a 28 day cycle<br>* Other names: Taxol;Drug: Placebo<br>* 100mg BID oral tablet to match olaparib tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) in the Overall Study Population | 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. | 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 | 
| Progression Free Survival (PFS) in Patients With Tumours Defined as Homologous Recombination Deficient by Loss of Ataxia-Telangiectasia Mutation (ATM) Protein [ATM Negative Patients] | 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. | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) in the Overall Study Population | 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. | 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 (OS) in ATM Negative Patients | 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. | 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 | 
| Objective Response Rate (ORR) in the Overall Study Population | 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). | 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 (ORR) in the ATM Negative Patients | 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). | 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 | 
| Percentage Change in Tumour Size at Week 8 in the Overall Study Population | Percentage change in tumour size from baseline to Week 8 calculated as 100 X (week 8 tumour size - baseline tumour size) / (baseline tumour size) | Tumour scans done at Baseline and week 8 | 
| Percentage Change in Tumour Size at Week 8 in the ATM Negative Patients | Percentage change in tumour size from baseline to Week 8 calculated as 100 X (week 8 tumour size - baseline tumour size) / (baseline tumour size) | Tumour scans done at Baseline and week 8 | 
| Time to Deterioration in Global Quality of Life (QoL) Score in the Overall Study Population | Time calculated from randomisation till worsening of Global QoL score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data | Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months | 
| Time to Deterioration in QoL Fatigue Score in the Overall Study Population | Time calculated from randomisation till worsening of fatigue score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data | Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months | 
| Time to Deterioration in QoL Nausea & Vomiting Domain Score in the Overall Study Population | Time calculated from randomisation till worsening of nausea & vomiting domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data | Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months | 
| Time to Deterioration in QoL Pain Domain Score in the Overall Study Population | Time calculated from randomisation till worsening of pain domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data | Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months | 
| Time to Deterioration in QoL Dysphagia Domain Score in the Overall Study Population | Time calculated from randomisation till worsening of dysphagia domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data | Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months | 
| Time to Deterioration in QoL Eating Restriction Domain Score in the Overall Study Population | Time calculated from randomisation till worsening of eating restriction domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data | Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months | 
| Time to Deterioration in QoL Stomach Pain Domain Score in the Overall Study Population | Time calculated from randomisation till worsening of stomach pain domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data | Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months | 
| Time to Deterioration in QoL Reflux Domain Score in the Overall Study Population | Time calculated from randomisation till worsening of reflux domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data | Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months | 
| Time to Deterioration in QoL Anxiety Domain Score in the Overall Study Population | Time calculated from randomisation till worsening of anxiety domain score based on European Organisation for Research and Treatment of Cancer (EORTC) questionnaire data | Questionnaire data collected at Baseline ie on or before date of randomisation, every 4 weeks post baseline, assessed maximum up to 27 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Poly(ADP ribose), polymerase (PARP), Gastric cancer, olaparib, PARP inhibitor, ATM AZD2281, Ku0059436, Homologous Recombination deficiency (HRD), Recurrent gastric cancer, metastatic gastric cancer