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A Randomised, Double-blind, Parallel Group, Placebo-controlled Multi-centre Phase III Study to Assess the Efficacy and Safety of Olaparib Versus Placebo as Adjuvant Treatment in Patients With gBRCA1/2 Mutations and High Risk HER2 Negative Primary Breast Cancer Who Have Completed Definitive Local Treatment and Neoadjuvant or Adjuvant Chemotherapy

Primary Objective The primary objective is to assess the effect of adjuvant treatment with olaparib on Invasive Disease Free Survival (IDFS) Safety Objective To assess the safety and tolerability of adjuvant treatment with olaparib Secondary Objectives 1. To assess the effect of adjuvant treatment with olaparib on overall survival (OS) 2. To assess the effect of adjuvant treatment with olaparib on Distant Disease Free Survival (DDFS) 3. To assess the effect of adjuvant treatment with olaparib on the incidence of new primary contralateral invasive breast cancer, primary contralateral non-invasive breast cancer, new primary ovarian cancer, new primary fallopian tube cancer and new primary peritoneal cancer. 4. To assess the effect of olaparib on patient reported outcomes using the FACIT-Fatigue and EORTC QLQ-C30 questionnaires 5. To assess the efficacy of olaparib in patients identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future germline BRCA mutation assays (gene sequencing and large rearrangement analysis) 6. To determine the exposure to olaparib (in plasma) in patients receiving olaparib as adjuvant therapy. Exploratory Objectives The exploratory objectives of this study are: 1. To assess the consistency of treatment effects on efficacy endpoints across potential or expected prognostic factors, including the baseline stratification factors with special emphasis on hormone receptor status 2. To explore methods for estimating overall survival (OS) adjusting for the impact of confounding by subsequent therapies, specifically the control arm receiving subsequent Polyadenosine 5 diphosphoribose [poly (ADP ribose)] polymerisation (PARP) inhibitors or platinum salts 3. To explore whether resistance mechanisms to olaparib can be identified through analysis of tumour and blood sample derivatives (cells, plasma and protein and nucleicacid derivatives) - archival tumour samples (mandatory*), tumour biopsy at recurrence (optional) and blood samples at baseline, 30 days post study treatment and on disease recurrence (mandatory) *For adjuvant patients this refers to the surgical specimen; for neoadjuvant patients, both the pre-treatment biopsy and the surgical specimen with residual disease specimen are requested, but only one is mandatory. If the surgery tumour blocks are available, but cannot be submitted, sites may submit a portion of invasive tumour from the original block, either by taking at least one core of at least 3 mm in diameter, or by splitting the original block in two parts, and re-embedding one in a new block for central submission. If blocks containing pre-neoadjuvant treatment core biopsies are available but cannot be submitted, sections mounted on glass slides prepared from the block can be provided. If tumour sample can't be provided as requested above or if it's not available, approval by Study Team for patient's entry into the trial is required. 4. To determine the frequency of and describe the nature of BRCA mutation/s in tumour samples and to compare this with germline BRCA mutation status 5. Future exploratory research into factors that may influence development of cancer and/or response to treatment (where response is defined broadly to include efficacy, tolerability or safety) may be performed on the collected and stored tumour and blood samples 6. To collect and store DNA according to each country s local and ethical procedures for future exploratory research into genes/genetic variation that may influence response (i.e. distribution, safety, tolerability and efficacy) to study treatments and/or susceptibility to disease (optional)

Primary Objective The primary objective is to assess the effect of adjuvant treatment with olaparib on Invasive Disease Free Survival (IDFS) Safety Objective To assess the safety and tolerability of adjuvant treatment with olaparib Secondary Objectives 1. To assess the effect of adjuvant treatment with olaparib on overall survival (OS) 2. To assess the effect of adjuvant treatment with olaparib on Distant Disease Free Survival (DDFS) 3. To assess the effect of adjuvant treatment with olaparib on the incidence of new primary contralateral invasive breast cancer, primary contralateral non-invasive breast cancer, new primary ovarian cancer, new primary fallopian tube cancer and new primary peritoneal cancer. 4. To assess the effect of olaparib on patient reported outcomes using the FACIT-Fatigue and EORTC QLQ-C30 questionnaires 5. To assess the efficacy of olaparib in patients identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future germline BRCA mutation assays (gene sequencing and large rearrangement analysis) 6. To determine the exposure to olaparib (in plasma) in patients receiving olaparib as adjuvant therapy. Exploratory Objectives The exploratory objectives of this study are: 1. To assess the consistency of treatment effects on efficacy endpoints across potential or expected prognostic factors, including the baseline stratification factors with special emphasis on hormone receptor status 2. To explore methods for estimating overall survival (OS) adjusting for the impact of confounding by subsequent therapies, specifically the control arm receiving subsequent Polyadenosine 5 diphosphoribose [poly (ADP ribose)] polymerisation (PARP) inhibitors or platinum salts 3. To explore whether resistance mechanisms to olaparib can be identified through analysis of tumour and blood sample derivatives (cells, plasma and protein and nucleicacid derivatives) - archival tumour samples (mandatory*), tumour biopsy at recurrence (optional) and blood samples at baseline, 30 days post study treatment and on disease recurrence (mandatory) *For adjuvant patients this refers to the surgical specimen; for neoadjuvant patients, both the pre-treatment biopsy and the surgical specimen with residual disease specimen are requested, but only one is mandatory. If the surgery tumour blocks are available, but cannot be submitted, sites may submit a portion of invasive tumour from the original block, either by taking at least one core of at least 3 mm in diameter, or by splitting the original block in two parts, and re-embedding one in a new block for central submission. If blocks containing pre-neoadjuvant treatment core biopsies are available but cannot be submitted, sections mounted on glass slides prepared from the block can be provided. If tumour sample can't be provided as requested above or if it's not available, approval by Study Team for patient's entry into the trial is required. 4. To determine the frequency of and describe the nature of BRCA mutation/s in tumour samples and to compare this with germline BRCA mutation status 5. Future exploratory research into factors that may influence development of cancer and/or response to treatment (where response is defined broadly to include efficacy, tolerability or safety) may be performed on the collected and stored tumour and blood samples 6. To collect and store DNA according to each country s local and ethical procedures for future exploratory research into genes/genetic variation that may influence response (i.e. distribution, safety, tolerability and efficacy) to study treatments and/or susceptibility to disease (optional)