Open Label Study to Assess Efficacy and Safety of Olaparib in Confirmed Genetic BRCA1 or BRCA2 Mutation Pats

Study Overview
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Brief Summary
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To assess the efficacy of oral olaparib in patients with advanced cancer who have a confirmed genetic BRCA1 and/or BRCA2 mutation, by assessment of tumour response

Official Title
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A Phase II, Open Label, Non Randomised, Non Comparative, Multicentre Study to Assess the Efficacy and Safety of Olaparib Given Orally Twice Daily in Patients With Advanced Cancers Who Have a Confirmed Genetic BRCA 1 and/or BRCA2 Mutation

Conditions
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Ovarian, Breast, Prostate, Pancreatic, Advanced Tumours

Intervention / Treatment
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* Drug: olaparib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed documented deleterious or suspected deleterious BRCA mutation. (The presence of a loss-of-function germline mutation in the BRCA1 and/or BRCA2 gene must be confirmed prior to consent according to local practice). Confirmed malignant solid tumours for which no standard treatment exists At least one lesion (measurable and/or non measurable) at baseline that can be accurately assessed by CT/MRI and is suitable for repeated assessment at follow up visits Exclusion Criteria: Any previous treatment with a PARP inhibitor, including olaparib Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication Patients receiving any systematic chemotherapy, radiotherapy (except for palliative reasons) within 2 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used)

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Olaparib is available as a film-coated tablet containing 150 mg or 100 mg of olaparib. Subjects will be administered study treatment orally at a dose recommended by Investigator. Full dose: 300 mg twice daily (bid) or Reduced doses: 200 mg twice daily (bid) or 100 mg twice daily (bid). The planned dose of 300 mg bid will be made up of two x 150 mg tablets twice daily, with 100 mg tablets used to manage dose reductions. | Drug: olaparib<br>* Tablets Oral BID<br>* Other names: Lynparza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumour Response Rate | Tumour response rate is the proportion of patients 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 ie 28 days before first study drug dose and then every 8 weeks up to 6 months after starting study treatment, then every 12 weeks until objective disease progression, assessed maximum up to 29 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | 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 ie 28 days before first study drug dose and then every 8 weeks up to 6 months after starting study treatment, then every 12 weeks until objective disease progression, assessed maximum up to 29 months | 
| Progression Free Survival | Progression free survival is defined as the duration from first dose till objective progression or death. In absence of progression or death, the time is calculated from first dose till last evaluable scanning visit. | Tumour assessments are carried out at baseline ie 28 days before first study drug dose and then every 8 weeks up to 6 months after starting study treatment, then every 12 weeks until objective disease progression, assessed maximum up to 29 months | 
| Overall Survival | Overall survival is defined as the duration from first dose till death. In absence of death, the time is calculated from first dose till the date subject last known to be alive. | Survival follow-up from first dose till death of the patient or till end of study in absence of death, assessed maximum up to 29 months | 
| Overall Survival Rate at 12 Months | Overall survival rate at 12 months is defined as the proportion of patients who are alive 12 months after date of first dose | Survival follow-up from first dose till death of the patient or till end of study in absence of death, assessed maximum up to 29 months | 
| Duration of Response | Duration of response is calculated from the date of first documented response (complete or partial) until date of documented progression (as defined by RECIST 1.1) or death (by any cause) in the absence of disease progression. | From onset of first occurrence of complete or partial response till documented progression or death by any cause in the absence of progression, assessed maximum up to 29 months | 
| Disease Control Rate at Week 16 | Disease control rate is the proportion of patients with best response of complete or partial response or stable disease according to definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) till week 16. | Tumour assessments carried out at baseline ie 28 days before first study drug dose and then at week 8 and week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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olaparib, PARP inhibitors, genetic BRCA1 mutation, BRCA2 mutation, solid tumour refractory