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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer Metastatic; BRCA 1 Gene Mutation; BRCA 2 Gene Mutation
• Intervention / Treatment: Drug: Olaparib; Drug: Physician's choice chemotherapy

• Study Type: Interventional
• Enrollment (Actual): 302
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • Research Site
  • Plovdiv, Bulgaria, 4004
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  • Sofia, Bulgaria, 1233
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  • Sofia, Bulgaria, 1330
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  • Sofia, Bulgaria, 1303
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  • Sofia, Bulgaria, 1504
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  • Varna, Bulgaria, 9010
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  • Vratza, Bulgaria, 3000
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• China
  • Beijing, China, 100142
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  • Beijing, China, 100021
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  • Beijing, China, 100006
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  • Changchun, China, 130061
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  • Changsha, China, 410013
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  • Chengdu, China, 610041
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  • Dalian, China, 116011
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  • Guangzhou, China, 510060
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  • Hangzhou, China, 310022
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  • Harbin, China, 150081
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  • Nanjing, China, 210009
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  • Shanghai, China, 200032
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  • Shanghai, China, 200025
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  • Shenyang, China, 110016
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  • Tianjin, China, 300060
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• Czechia
  • Brno, Czechia, 656 53
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  • Olomouc, Czechia, 775 20
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  • Praha 2, Czechia, 128 08
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• France
  • Caen Cedex, France, 14076
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  • Montpellier, France, 34298
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  • Rouen, France, 76038
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  • Strasbourg Cedex, France, 67065
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  • Villejuif, France, 94800
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• Hungary
  • Budapest, Hungary, 1083
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  • Budapest, Hungary, 1115
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  • Budapest, Hungary, 1145
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  • Budapest, Hungary, 1122
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  • Budapest, Hungary, 1032
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  • Nyíregyháza, Hungary, 4400
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  • Veszprém, Hungary, 8200
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• Italy
  • Bologna, Italy, 40138
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  • Napoli, Italy, 80131
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  • Padova, Italy, 35128
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  • Roma, Italy, 00168
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  • Roma, Italy, 00144
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  • Rozzano, Italy, 20089
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• Japan
  • Chuo-ku, Japan, 104-0045
    • Research Site
  • Chuo-ku, Japan, 104-8560
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  • Fukuoka-shi, Japan, 811-1395
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  • Kagoshima-shi, Japan, 892-0833
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  • Nagoya-shi, Japan, 464-8681
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  • Osaka-city, Japan, 540-0006
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  • Sapporo-shi, Japan, 003-0804
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  • Shinagawa-ku, Japan, 142-8666
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  • Suita-city, Japan, 565-0871
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• Korea, Republic of
  • Cheongju-si, Korea, Republic of, 28644
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  • Daegu, Korea, Republic of, 41404
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  • Incheon, Korea, Republic of, 21565
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  • Seongnam-si, Korea, Republic of, 13620
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  • Seoul, Korea, Republic of, 03722
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  • Seoul, Korea, Republic of, 03080
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  • Seoul, Korea, Republic of, 158-710
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  • Seoul, Korea, Republic of, 6351
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• Mexico
  • Estado de México, Mexico, 50080
    • Research Site
  • Merida, Mexico, 97000
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  • Merida, Mexico, 97133
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  • Mexico, Mexico, 6760
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  • Mérida, Mexico, 97070
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  • San Juan del Rio, Mexico, 76800
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• Peru
  • Cusco, Peru, CUSCO 01
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  • Lima, Peru, LIMA 27
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  • Lima, Peru, LIMA 34
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  • Lima, Peru, LIMA 41
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  • Lima, Peru, LIMA 01
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  • Lima, Peru, Lima 18
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  • San Borja, Peru, LIMA 41
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• Poland
  • Elbląg, Poland, 82-300
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  • Gdańsk, Poland, 80-214
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  • Grzepnica, Poland, 72-003
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  • Tarnobrzeg, Poland, 39-400
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  • Warszawa, Poland, 03-291
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  • Warszawa, Poland, 01-748
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  • Łódź, Poland, 93-513
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• Romania
  • Bucharest, Romania, 013811
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  • Bucuresti, Romania, 011171
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  • Bucuresti, Romania, 030171
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  • Cluj Napoca, Romania, 400015
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  • Cluj-Napoca, Romania, 400015
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• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
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  • Ivanovo, Russian Federation, 153040
    • Research Site
  • Moscow, Russian Federation, 115478
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  • Omsk, Russian Federation, 644013
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  • Saint Petersburg, Russian Federation, 195271
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  • Saint Petersburg, Russian Federation, 197022
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  • Saint Petersburg, Russian Federation, 195257
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  • Saransk, Russian Federation, 430005
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  • St-Petersburg, Russian Federation, 197758
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  • St.Petersburg, Russian Federation, 191014
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  • Yaroslavl, Russian Federation, 150054
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• Spain
  • Barcelona, Spain, 08003
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  • Córdoba, Spain, 14004
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  • Granada, Spain, 18014
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  • Madrid, Spain, 28034
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  • Majadahonda, Spain, 28222
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  • Oviedo, Spain, 33011
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  • Sevilla, Spain, 41013
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  • Valencia, Spain, 46026
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  • Zaragoza, Spain, 50009
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• Switzerland
  • Bern, Switzerland, CH-3010
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  • Lausanne, Switzerland, CH-1011
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  • Zürich, Switzerland, 8063
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• Taiwan
  • Kaohsiung, Taiwan, 80756
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  • Taichung, Taiwan, 407
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  • Taipei, Taiwan, 10449
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  • Taipei, Taiwan, 11217
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  • Taipei, Taiwan, 10048
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  • Taoyuan, Taiwan, 333
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• Turkey
  • Adana, Turkey, 1260
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  • Ankara, Turkey, 06230
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  • Edirne, Turkey, 22030
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  • Gaziantep, Turkey, 27310
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  • Istanbul, Turkey, 34390
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  • Izmir, Turkey, 35100
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  • Kayseri, Turkey, 38039
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  • Konya, Turkey, 42080
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  • Mersin, Turkey, 33110
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• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
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  • Colchester, United Kingdom, CO4 5JL
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  • Coventry, United Kingdom, CV2 2DX
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  • London, United Kingdom, W6 8RF
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  • Manchester, United Kingdom, M20 4BX
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  • Plymouth, United Kingdom, PL6 8DH.
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• United States
  • California
    • San Diego, California, United States, 92123
      • Research Site
    • Santa Rosa, California, United States, 95403
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    • Whittier, California, United States, 90602
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  • Colorado
    • Denver, Colorado, United States, 80204
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  • Connecticut
    • New Haven, Connecticut, United States, 06510
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  • District of Columbia
    • Washington, District of Columbia, United States, 20007
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  • Florida
    • Jacksonville, Florida, United States, 32224
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    • Orlando, Florida, United States, 32804
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    • Plantation, Florida, United States, 33324
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  • Georgia
    • Columbus, Georgia, United States, 31904
      • Research Site
    • Marietta, Georgia, United States, 30060
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  • Illinois
    • Chicago, Illinois, United States, 60612
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    • Niles, Illinois, United States, 60714
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  • Kansas
    • Wichita, Kansas, United States, 67214
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  • Louisiana
    • Lafayette, Louisiana, United States, 70506
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  • Massachusetts
    • Boston, Massachusetts, United States, 02114
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    • Boston, Massachusetts, United States, 02215
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    • Boston, Massachusetts, United States, 02118
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  • Michigan
    • Detroit, Michigan, United States, 48201
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    • Grand Rapids, Michigan, United States, 49503
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  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
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    • Saint Louis Park, Minnesota, United States, 55416
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  • Mississippi
    • Jackson, Mississippi, United States, 39202
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  • Missouri
    • Columbia, Missouri, United States, 65212
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    • Saint Louis, Missouri, United States, 63131
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  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
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  • New York
    • Commack, New York, United States, 11725
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    • Harrison, New York, United States, 10604
      • Research Site
    • New York, New York, United States, 10021
      • Research Site
    • New York, New York, United States, 10065
      • Research Site
    • Rockville Centre, New York, United States, 11570
      • Research Site
    • Syracuse, New York, United States, 13210
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Research Site
    • Cleveland, Ohio, United States, 44195
      • Research Site
    • Cleveland, Ohio, United States, 44106
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  • Oregon
    • Portland, Oregon, United States, 97213
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  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
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    • Sayre, Pennsylvania, United States, 18840
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  • Tennessee
    • Germantown, Tennessee, United States, 38138
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  • Texas
    • Houston, Texas, United States, 77030
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    • Tyler, Texas, United States, 75701
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  • Vermont
    • Burlington, Vermont, United States, 05401
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Outcome Measure	Measure Description	Time Frame
Time to Second Progression or Death (PFS2)	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.	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.
Overall Survival (OS)	Time from randomisation until death due to any cause.	Survival status reviewed every 3 weeks until treatment discontinued, then every 8 weeks. Assessed up to a maximum of 30 months.
Objective Response Rate (ORR) Using Blinded Independent Central Review (BICR) Data Assessed by Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1)	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.	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.
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)	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.	EORTC QLQ-C30 assessments performed at baseline then every ~6 weeks until objective radiological disease progression. Assessed up to a maximum of 30 months.
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 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).	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.
Overall Survival (OS) at Final OS	Time from randomisation until death due to any cause.	Survival status reviewed every 3 weeks until treatment discontinued, then every 8 weeks. Assessed up to a maximum of 40 months.
Overall Survival (OS) at Extended OS	Time from randomisation until death due to any cause.	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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Subsequent Cancer Therapy or Death (TFST)	Time from randomisation to the earliest of first subsequent cancer therapy start date following study treatment discontinuation, or death.	Subsequent cancer therapy status reviewed every 8 weeks following study treatment discontinuation. Assessed up to a maximum of 30 months.
Time to Second Subsequent Cancer Therapy or Death (TSST)	Time from randomisation to the earliest of second subsequent cancer therapy start date following study treatment discontinuation, or death.	Subsequent cancer therapy status reviewed every 8 weeks following study treatment discontinuation. Assessed up to a maximum of 30 months.
Time to First Subsequent Cancer Therapy or Death (TFST) at Extended OS	Time from randomisation to the earliest of first subsequent cancer therapy start date following study treatment discontinuation, or death.	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 to Second Subsequent Cancer Therapy or Death (TSST) at Extended OS	Time from randomisation to the earliest of second subsequent cancer therapy start date following study treatment discontinuation, or death.	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.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Merck Sharp & Dohme LLC; Myriad Genetic Laboratories, Inc.
• Investigators: Principal Investigator: Mark Robson, MD, Memorial Sloan-Kettering Cancer Center, New York

Publications and helpful links

General Publications

• 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.

Helpful Links

• Redacted Protocol

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2014
• Primary Completion (Actual): December 9, 2016
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: November 18, 2013
• First Submitted That Met QC Criteria: November 27, 2013
• First Posted (Estimated): December 4, 2013

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Breast Cancer; chemotherapy; HER2; PARP inhibitor; Metastatic; Olaparib; BRCA
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Olaparib
• Other Study ID Numbers: D0819C00003; 2013-005137-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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
• IPD Sharing 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
• IPD Sharing 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP