NCT02000622 · CITED IN SOURCE DOCUMENTS

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.

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2026-02-13

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression-free Survival (PFS) Using Blinded Independent Central Review (BICR) According to Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1)

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outcome · POSTED

Time to Second Progression or Death (PFS2)

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Objective Response Rate (ORR) Using Blinded Independent Central Review (BICR) Data Assessed by Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1)

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outcome · POSTED

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)

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outcome · POSTED

Progression-free Survival (PFS) Using Blinded Independent Central Review (BICR) According to Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1) in Patients Confirmed as Myriad CDx gBRCAm

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outcome · POSTED

Time to First Subsequent Cancer Therapy or Death (TFST)

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outcome · POSTED

Time to Second Subsequent Cancer Therapy or Death (TSST)

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outcome · POSTED

Overall Survival (OS) at Final OS

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outcome · POSTED

Overall Survival (OS) at Extended OS

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outcome · POSTED

Time to First Subsequent Cancer Therapy or Death (TFST) at Extended OS

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outcome · POSTED

Time to Second Subsequent Cancer Therapy or Death (TSST) at Extended OS

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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.
healthy Volunteers: false
maximum Age: 99 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Olaparib tablet 300mg bd po
intervention Names
Drug: Olaparib
label
Olaparib
type
EXPERIMENTAL
description
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
intervention Names
Drug: Physician's choice chemotherapy
label
Physician's choice chemotherapy
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Olaparib
description
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.
name
Olaparib
type
DRUG
arm Group Labels
Physician's choice chemotherapy
description
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
name
Physician's choice chemotherapy
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 302
type: ACTUAL

Registered outcome plans (not posted results)

other Outcomes

description
Time from randomisation to the earliest of first subsequent cancer therapy start date following study treatment discontinuation, or death.
measure
Time to First Subsequent Cancer Therapy or Death (TFST)
time Frame
Subsequent cancer therapy status reviewed every 8 weeks following study treatment discontinuation. Assessed up to a maximum of 30 months.
description
Time from randomisation to the earliest of second subsequent cancer therapy start date following study treatment discontinuation, or death.
measure
Time to Second Subsequent Cancer Therapy or Death (TSST)
time Frame
Subsequent cancer therapy status reviewed every 8 weeks following study treatment discontinuation. Assessed up to a maximum of 30 months.
description
Time from randomisation to the earliest of first subsequent cancer therapy start date following study treatment discontinuation, or death.
measure
Time to First Subsequent Cancer Therapy or Death (TFST) at Extended OS
time Frame
Subsequent cancer therapy status reviewed every 8 weeks following study treatment discontinuation until Sep 2017 (final OS DCO), then every 3 months. Assessed up to a maximum of 64 months.
description
Time from randomisation to the earliest of second subsequent cancer therapy start date following study treatment discontinuation, or death.
measure
Time to Second Subsequent Cancer Therapy or Death (TSST) at Extended OS
time Frame
Subsequent cancer therapy status reviewed every 8 weeks following study treatment discontinuation until Sep 2017 (final OS DCO), then every 3 months. Assessed up to a maximum of 64 months.

primary Outcomes

description
Time from randomisation to the earliest of objective radiological progression or death by any cause in the absence of objective progression. Objective radiological progression is defined using Response Evaluation Criteria In Solid Tumours (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
measure
Progression-free Survival (PFS) Using Blinded Independent Central Review (BICR) According to Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1)
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.

secondary Outcomes

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. Objective radiological progression is defined using Response Evaluation Criteria In Solid Tumours (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Symptomatic progression is assessed by investigators based on clinical examination.
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.
description
Time from randomisation until death due to any cause.
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.
description
Number of responders according to blinded independent central review (BICR) assessment. Per Response Evaluation Criteria In Solid Tumours Criteria (RECIST v1.1) for target lesions assessed by CT or MRI: Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response = CR + PR.
measure
Objective Response Rate (ORR) Using Blinded Independent Central Review (BICR) Data Assessed by Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1)
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.
description
Change from baseline in global health status/quality of life (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
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.
description
Time from randomisation to the earliest of objective radiological progression or death by any cause in the absence of objective progression. Objective radiological progression is defined using Response Evaluation Criteria In Solid Tumours Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Assessed 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).
measure
Progression-free Survival (PFS) Using Blinded Independent Central Review (BICR) According to Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1) 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.
description
Time from randomisation until death due to any cause.
measure
Overall Survival (OS) at Final OS
time Frame
Survival status reviewed every 3 weeks until treatment discontinued, then every 8 weeks. Assessed up to a maximum of 40 months.
description
Time from randomisation until death due to any cause.
measure
Overall Survival (OS) at Extended OS
time Frame
Survival status reviewed every 3 weeks until treatment discontinued, then every 8 weeks until Sep 2017 (final OS DCO), then every 3 months. Assessed up to a maximum of 64 months.

Full study description

brief 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.

Source references

references

citation
Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. doi: 10.1056/NEJMoa1706450. Epub 2017 Jun 4.
pmid
28578601
type
DERIVED