Overview

This trial is active, not recruiting.

Conditions breast cancer metastatic, brca 1 gene mutation, brca 2 gene mutation
Treatments olaparib, physician's choice chemotherapy
Phase phase 3
Targets BRCA, PARP
Sponsor AstraZeneca
Collaborator Myriad Genetic Laboratories, Inc.
Start date March 2014
End date January 2017
Trial size 310 participants
Trial identifier NCT02000622, 2013-005137-20, D0819C00003

Summary

This open label, randomised, controlled, multi-centre phase III study will assess the efficacy and safety of single agent olaparib vs standard of care based on physician's choice of capecitabine, vinorelbine or eribulin in metastatic breast cancer patients with gBRCA 1/2 mutations.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Olaparib tablet 300mg bd po
olaparib
Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
(Active Comparator)
Capecitabine 2500 mg/m2 d1-14 q 21, or Vinorelbine 30 mg/m2 d1,8 q 21, or Eribulin 1.4 mg/m2 d1,8 q 21
physician's choice chemotherapy
Investigators will declare one of the following regimens: Capecitabine 2500 mg/m2 po daily (divided in 2 doses) x 14 days, repeat every 21 days Vinorelbine 30 mg/m2 IV Day 1 and Day 8, repeat every 21 days Eribulin 1.4 mg/m2 IV Day 1 and Day 8, repeat every 21 days

Primary Outcomes

Measure
Progression Free Survival by BICR using RECIST 1.1.
time frame: Assessed when approx 75% patients have experienced objective disease progression by RECIST. RECIST assessments performed at baseline, every 6 wks for the first 6 mths, then every 12 wks until progression. Data collection will last up to approx 7 years.

Secondary Outcomes

Measure
Overall Survival
time frame: Assessed at time of PFS analysis and when approx 60% patients have died by any cause (on average 15 months after randomisation). Survival assessed every 8 weeks following objective disease progression. Data collection will last up to approx 7 years.
Time from randomisation to second progression or death (PFS2).
time frame: Assessed at time of PFS analysis and at final OS analysis. After first objective disease progression by RECIST, patients will then be assessed every 8 weeks for second progression. Data collection will last up to approx 7 years.
Objective Response Rate by BICR using RECIST 1.1
time frame: Assessed at time of PFS analysis. RECIST assessments are performed at baseline, every 6 weeks for the first 6 months, then every 12 weeks until objective disease progression. Data collection will last up to approx 7 years.
Adjusted mean change from baseline in global QoL score from the EORTC-QLQ-C30 questionnaire.
time frame: EORTC QLQ-C30 questionnaires to be completed at baseline and every 6 weeks until disease progression. Study data collection is expected to last up to approximately 7 years.
Safety and tolerability of olaparib by assessment of adverse events.
time frame: Adverse events collected from informed consent until post treatment 30-day follow-up period. Study data collection is expected to last up to approximately 7 years.
Safety and tolerability of olaparib by assessment of physical examination.
time frame: Physical examinations carried out at baseline and until study treatment discontinued and at the post treatment 30-day follow-up visit. Study data collection is expected to last up to approximately 7 years.
Safety and tolerability of olaparib by assessment of vital signs.
time frame: Vital signs assessments collected at baseline and until study treatment discontinued and at the post treatment 30-day follow-up visit. Study data collection is expected to last up to approximately 7 years.
Safety and tolerability of olaparib by assessment of laboratory parameters.
time frame: Laboratory parameter assessments collected at baseline and until study treatment discontinued and at the post treatment 30-day follow-up visit. Study data collection is expected to last up to approximately 7 years.

Eligibility Criteria

Male or female participants from 18 years up to 99 years old.

Inclusion Criteria: - Germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious. - Histologically or cytologically confirmed breast cancer with evidence of metastatic disease. - Prior therapy with an anthracycline and a taxane in either an adjuvant or metastatic setting. - Prior platinum allowed as long as no breast cancer progression occurred on treatment or if given in adjuvant/neoadjuvant setting at least 12 months from last dose to study entry elapsed. - ER/PR breast cancer positive patients must have received and progressed on at least one endocrine therapy (adjuvant or metastatic), or have disease that the treating physician believes to be inappropriate for endocrine therapy. - ECOG performance status 0-1. - Adequate bone marrow, kidney and liver function. Exclusion Criteria: - Prior treatment with PARP inhibitor. - Patients with HER2 positive disease. - More than 2 prior lines of chemotherapy for metastatic breast cancer. - Untreated and/or uncontrolled brain metastases. - Prior malignancy unless curatively treated and disease-free for > 5 years prior to study entry. Prior adequately treated non-melanoma skin cancer, in situ cancer of the cervix, DCIS or stage I grade 1 endometrial cancer allowed. - Known HIV (Human Immunodeficiency Virus) infection. - Pregnant or breast-feeding women.

Additional Information

Official title A Phase III, Open Label, Randomised, Controlled, Multi-centre Study to Assess the Efficacy and Safety of Olaparib Monotherapy Versus Physicians Choice Chemotherapy in the Treatment of Metastatic Breast Cancer Patients With Germline BRCA1/2 Mutations.
Principal investigator Mark Robson, MD
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by AstraZeneca.