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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by AstraZeneca
Sponsor:
Collaborator:
Myriad Genetics - BRAC Analysis test for FDA Premarket Approval (PMA)
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02000622
First received: November 18, 2013
Last updated: September 16, 2014
Last verified: September 2014
  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.


Condition Intervention Phase
Breast Cancer Metastatic
Drug: Olaparib
Drug: Physician's choice chemotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    Efficacy of single agent olaparib vs physician's choice chemotherapy (capecitabine, vinorelbine or eribulin) by assessment of progression free survival (PFS) using blinded independent central review (BICR) data assessed by Response Evaluation Criteria in Solid Tumours (RECIST 1.1).


Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    Efficacy of single agent olaparib vs physician's choice chemotherapy (capecitabine, vinorelbine or eribulin) by assessment of overall survival (OS). This assessment is performed until the time of the final OS analysis (when approximately 60% patients have died).

  • 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. ] [ Designated as safety issue: No ]
    Efficacy of single agent olaparib vs physician's choice chemotherapy (capecitabine, vinorelbine or eribulin) by assessment of time to second progression, defined as objective radiological or symptomatic progression, or death (PFS2). This assessment is performed until the time of the final OS analysis (when approximately 60% patients have died).

  • 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. ] [ Designated as safety issue: No ]
    Efficacy of single agent olaparib vs physician's choice chemotherapy (capecitabine, vinorelbine or eribulin) by assessment of objective response rate (ORR) using BICR data assessed by RECIST 1.1.

  • 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. ] [ Designated as safety issue: No ]
    Assessment of the effect of olaparib on the Health-related Quality of Life (HRQoL) as measured by EORTC QLQ-C30 global QoL scale.

  • 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. ] [ Designated as safety issue: Yes ]
    Assessment of adverse events (AEs), graded by CTCAE (v4.0).

  • 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. ] [ Designated as safety issue: Yes ]
    Assessment of physical examination.

  • 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. ] [ Designated as safety issue: Yes ]
    Assessment of vital signs including blood pressure (BP), pulse and electrocardiogram (ECG).

  • 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. ] [ Designated as safety issue: Yes ]
    Assessment of laboratory parameters including clinical chemistry and haematology.


Estimated Enrollment: 2820
Study Start Date: March 2014
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02000622

Contacts
Contact: Tsveta Milenkova; Jane Robertson +44 (0) 1625 518869 ClinicalTrialTransparency@astrazeneca.com
Contact: Cancer Study Locator 877 400 4656 AstraZeneca@emergingmed.com

  Show 108 Study Locations
Sponsors and Collaborators
AstraZeneca
Myriad Genetics - BRAC Analysis test for FDA Premarket Approval (PMA)
Investigators
Principal Investigator: Mark Robson, MD Memorial Sloan-Kettering Cancer Center, New York
  More Information

Additional Information:
No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02000622     History of Changes
Other Study ID Numbers: D0819C00003, 2013-005137-20
Study First Received: November 18, 2013
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
European Union: European Medicines Agency

Keywords provided by AstraZeneca:
Breast Cancer
Metastatic Breast Cancer
Olaparib
BRCA1/2 Mutations

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on September 18, 2014