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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. (OlympiAD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02000622
Recruitment Status : Active, not recruiting
First Posted : December 4, 2013
Results First Posted : December 22, 2017
Last Update Posted : February 28, 2023
Sponsor:
Collaborators:
Myriad Genetic Laboratories, Inc.
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
AstraZeneca

Study Description
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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.

Condition or disease Intervention/treatment Phase
Breast Cancer Metastatic BRCA 1 Gene Mutation BRCA 2 Gene Mutation Drug: Olaparib Drug: Physician's choice chemotherapy Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 302 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : March 27, 2014
Actual Primary Completion Date : December 9, 2016
Estimated Study Completion Date : December 29, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Olaparib

Arms and Interventions
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Arm Intervention/treatment
Experimental: Olaparib
Olaparib tablet 300mg bd po
 Drug: 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: Physician's choice chemotherapy
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
 Drug: 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


Outcome Measures
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Primary Outcome Measures :
  1. 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. ]
    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.


Secondary Outcome Measures :
  1. 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. ]
    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.

  2. 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. ]
    Time from randomisation until death due to any cause.

  3. 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. ]
    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.

  4. 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. ]
    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.

  5. 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. ]
    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).

  6. 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. ]
    Time from randomisation until death due to any cause.

  7. 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. ]
    Time from randomisation until death due to any cause.


Other Outcome Measures:
  1. 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. ]
    Time from randomisation to the earliest of first subsequent cancer therapy start date following study treatment discontinuation, or death.

  2. 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. ]
    Time from randomisation to the earliest of second subsequent cancer therapy start date following study treatment discontinuation, or death.

  3. 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. ]
    Time from randomisation to the earliest of first subsequent cancer therapy start date following study treatment discontinuation, or death.

  4. 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. ]
    Time from randomisation to the earliest of second subsequent cancer therapy start date following study treatment discontinuation, or death.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02000622


Locations
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Sponsors and Collaborators
AstraZeneca
Myriad Genetic Laboratories, Inc.
Merck Sharp & Dohme LLC
Investigators
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Principal Investigator: Mark Robson, MD Memorial Sloan-Kettering Cancer Center, New York
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02000622    
Other Study ID Numbers: D0819C00003
2013-005137-20 ( EudraCT Number )
First Posted: December 4, 2013    Key Record Dates
Results First Posted: December 22, 2017
Last Update Posted: February 28, 2023
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Keywords provided by AstraZeneca:
Breast Cancer
Metastatic
Olaparib
BRCA
 PARP inhibitor
HER2
chemotherapy
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
 Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents