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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)

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ClinicalTrials.gov Identifier: NCT02000622
Recruitment Status : Active, not recruiting
First Posted : December 4, 2013
Results First Posted : December 22, 2017
Last Update Posted : September 6, 2018
Sponsor:
Collaborators:
Myriad Genetic Laboratories, Inc.
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
AstraZeneca

November 18, 2013
December 4, 2013
November 28, 2017
December 22, 2017
September 6, 2018
March 27, 2014
December 9, 2016   (Final data collection date for primary outcome 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. ]
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.
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. ]
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).
Complete list of historical versions of study NCT02000622 on ClinicalTrials.gov Archive Site
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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. ]
    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. ]
    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. ]
    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. ]
    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. ]
    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. ]
    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. ]
    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. ]
    Assessment of laboratory parameters including clinical chemistry and haematology.
  • 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.
  • 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.
Not Provided
 
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.
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.
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.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Breast Cancer Metastatic
  • BRCA 1 Gene Mutation
  • BRCA 2 Gene Mutation
  • 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.
  • 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
  • Experimental: Olaparib
    Olaparib tablet 300mg bd po
    Intervention: Drug: Olaparib
  • 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
    Intervention: Drug: Physician's choice chemotherapy
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. Erratum in: N Engl J Med. 2017 Oct 26;377(17 ):1700.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
302
310
December 31, 2019
December 9, 2016   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years to 99 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Bulgaria,   China,   Czechia,   France,   Hungary,   Italy,   Japan,   Korea, Republic of,   Mexico,   Peru,   Poland,   Romania,   Russian Federation,   Spain,   Switzerland,   Taiwan,   Turkey,   United Kingdom,   United States
Czech Republic
 
NCT02000622
D0819C00003
2013-005137-20 ( EudraCT Number )
No
Not Provided
Not Provided
AstraZeneca
AstraZeneca
  • Myriad Genetic Laboratories, Inc.
  • Merck Sharp & Dohme Corp.
Principal Investigator: Mark Robson, MD Memorial Sloan-Kettering Cancer Center, New York
AstraZeneca
September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP