Clinical Trials /

Assessment of the Efficacy and Safety of Olaparib Monotherapy Versus Physicians Choice Chemotherapy in the Treatment of Metastatic Breast Cancer Patients With Germline BRCA1/2 Mutations.

NCT02000622

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Assessment of the Efficacy and Safety of Olaparib Monotherapy Versus Physicians Choice Chemotherapy in the Treatment of Metastatic Breast Cancer Patients With Germline BRCA1/2 Mutations.
  • 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.

Clinical Trial IDs

  • ORG STUDY ID: D0819C00003
  • SECONDARY ID: 2013-005137-20
  • NCT ID: NCT02000622

Conditions

  • Breast Cancer Metastatic
  • BRCA 1 Gene Mutation
  • BRCA 2 Gene Mutation

Interventions

DrugSynonymsArms
OlaparibOlaparib
Physician's choice chemotherapyPhysician's choice chemotherapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
OlaparibExperimentalOlaparib tablet 300mg bd po
  • Olaparib
Physician's choice chemotherapyActive ComparatorCapecitabine 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

Eligibility Criteria

        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.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free Survival (PFS) Using Blinded Independent Central Review (BICR) According to Modified Response Evaluation Criteria In Solid Tumours (RECIST 1.1)
Time Frame:Radiological scans performed at baseline then every ~6 weeks up to 24 weeks, then every ~ 12 weeks thereafter until objective radiological disease progression. Assessed up to a maximum of 30 months.
Safety Issue:
Description:Time from randomisation to the earliest of objective radiological progression (according to RECIST) or death by any cause in the absence of objective progression.

Secondary Outcome Measures

Measure:Time to Second Progression or Death (PFS2)
Time Frame:Second progression status reviewed every 8 weeks following the first objective radiological progression as per investigator assessment. Assessed up to a maximum of 30 months.
Safety Issue:
Description:Time from randomisation to the earliest of the progression event subsequent to the first objective radiological progression, or death. Second progression may involve any of; objective radiological or symptomatic progression or death.
Measure:Overall Survival (OS)
Time Frame:Survival status reviewed every 3 weeks until treatment discontinued, then every 8 weeks. Assessed up to a maximum of 30 months.
Safety Issue:
Description:Time from randomisation until death due to any cause.
Measure:Objective Response Rate (ORR) Using BICR Data Assessed by RECIST 1.1
Time Frame:Radiological scans performed at baseline then every ~6 weeks up to 24 weeks, then every ~ 12 weeks thereafter until objective radiological disease progression. Assessed up to a maximum of 30 months.
Safety Issue:
Description:Number of responders according to BICR assessment in the measurable disease population
Measure:Adjusted Mean Change in Global Health Status/Quality of Life (QoL) Score From the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC QLQ-C30)
Time Frame:EORTC QLQ-C30 assessments performed at baseline then every ~6 weeks until objective radiological disease progression. Assessed up to a maximum of 30 months.
Safety Issue:
Description:Change from baseline in global health status/QoL score assessed using a mixed model for repeated measures (MMRM) analysis, including all post-baseline global health status/QoL scores up to the latest scheduled visit where at least 20 patients on each treatment arm have a score. Global health status/QoL score is on a scale from 0 to 100. A higher score represents an improved health status/QoL.
Measure:Progression-free Survival (PFS) Using BICR According to Modified RECIST 1.1 in Patients Confirmed as Myriad CDx gBRCAm
Time Frame:Radiological scans performed at baseline then every ~6 weeks up to 24 weeks, then every ~ 12 weeks thereafter until objective radiological disease progression. Assessed up to a maximum of 30 months.
Safety Issue:
Description:Time from randomisation to the earliest of objective radiological progression (according to RECIST) or death by any cause in the absence of objective progression. Assessed in patients PFS using BICR according to modified RECIST 1.1 in patients with a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (gene sequencing and large rearrangement analysis)

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Breast Cancer
  • Metastatic
  • Olaparib
  • BRCA
  • PARP inhibitor
  • HER2
  • chemotherapy

Last Updated

November 28, 2017