ClinicalTrials.gov
ClinicalTrials.gov Menu

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 : September 6, 2018
Sponsor:
Collaborators:
Myriad Genetic Laboratories, Inc.
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
AstraZeneca

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 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 31, 2019

Resource links provided by the National Library of Medicine

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

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




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).


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.



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.


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.

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


  Hide Study Locations
Locations
United States, California
Research Site
San Diego, California, United States, 92123
Research Site
Santa Rosa, California, United States, 95403
Research Site
Whittier, California, United States, 90602
United States, Colorado
Research Site
Denver, Colorado, United States, 80204
United States, Connecticut
Research Site
New Haven, Connecticut, United States, 06510
United States, District of Columbia
Research Site
Washington, District of Columbia, United States, 20007
United States, Florida
Research Site
Jacksonville, Florida, United States, 32224
Research Site
Orlando, Florida, United States, 32804
Research Site
Plantation, Florida, United States, 33324
United States, Georgia
Research Site
Columbus, Georgia, United States, 31904
Research Site
Marietta, Georgia, United States, 30060
United States, Illinois
Research Site
Chicago, Illinois, United States, 60612
Research Site
Niles, Illinois, United States, 60714
United States, Kansas
Research Site
Wichita, Kansas, United States, 67214
United States, Louisiana
Research Site
Lafayette, Louisiana, United States, 70506
United States, Massachusetts
Research Site
Boston, Massachusetts, United States, 02114
Research Site
Boston, Massachusetts, United States, 02118
Research Site
Boston, Massachusetts, United States, 02215
United States, Michigan
Research Site
Detroit, Michigan, United States, 48201
Research Site
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
Research Site
Rochester, Minnesota, United States, 55905-0001
Research Site
Saint Louis Park, Minnesota, United States, 55416
United States, Mississippi
Research Site
Jackson, Mississippi, United States, 39202
United States, Missouri
Research Site
Columbia, Missouri, United States, 65212
Research Site
Saint Louis, Missouri, United States, 63131-2374
United States, New Hampshire
Research Site
Lebanon, New Hampshire, United States, 03756
United States, New York
Research Site
Commack, New York, United States, 11725
Research Site
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, 11788
Research Site
Syracuse, New York, United States, 13210
United States, Ohio
Research Site
Cincinnati, Ohio, United States, 45267
Research Site
Cleveland, Ohio, United States, 44106
Research Site
Cleveland, Ohio, United States, 44195
United States, Oregon
Research Site
Portland, Oregon, United States, 97213
United States, Pennsylvania
Research Site
Philadelphia, Pennsylvania, United States, 19104
Research Site
Sayre, Pennsylvania, United States, 18840
United States, Tennessee
Research Site
Germantown, Tennessee, United States, 38138
United States, Texas
Research Site
Houston, Texas, United States, 77030
Research Site
Tyler, Texas, United States, 75701
United States, Vermont
Research Site
Burlington, Vermont, United States, 05401
Bulgaria
Research Site
Plovdiv, Bulgaria, 4000
Research Site
Plovdiv, Bulgaria, 4004
Research Site
Sofia, Bulgaria, 1233
Research Site
Sofia, Bulgaria, 1303
Research Site
Sofia, Bulgaria, 1330
Research Site
Sofia, Bulgaria, 1504
Research Site
Varna, Bulgaria, 9010
Research Site
Vratza, Bulgaria, 3000
China
Research Site
Beijing, China, 100006
Research Site
Beijing, China, 100021
Research Site
Beijing, China, 100142
Research Site
Changchun, China, 130061
Research Site
Changsha, China, 410013
Research Site
Chengdu, China, 610041
Research Site
Dalian, China, 116011
Research Site
Guangzhou, China, 510060
Research Site
Hangzhou, China, 310022
Research Site
Harbin, China, 150081
Research Site
Nanjing, China, 210009
Research Site
Shanghai, China, 200025
Research Site
Shanghai, China, 200032
Research Site
Shenyang, China, 110016
Research Site
Tianjin, China, 300060
Czechia
Research Site
Brno, Czechia, 656 53
Research Site
Olomouc, Czechia, 775 20
Research Site
Praha 2, Czechia, 128 08
France
Research Site
Caen Cedex, France, 14076
Research Site
Montpellier, France, 34298
Research Site
Rouen, France, 76038
Research Site
Strasbourg Cedex, France, 67085
Research Site
Villejuif, France, 94800
Hungary
Research Site
Budapest, Hungary, 1032
Research Site
Budapest, Hungary, 1083
Research Site
Budapest, Hungary, 1115
Research Site
Budapest, Hungary, 1122
Research Site
Budapest, Hungary, 1145
Research Site
Nyíregyháza, Hungary, 4400
Research Site
Veszprém, Hungary, 8200
Italy
Research Site
Bologna, Italy, 40138
Research Site
Napoli, Italy, 80131
Research Site
Padova, Italy, 35128
Research Site
Roma, Italy, 00144
Research Site
Roma, Italy, 00168
Research Site
Rozzano, Italy, 20089
Japan
Research Site
Chuo-ku, Japan, 104-0045
Research Site
Chuo-ku, Japan, 104-8560
Research Site
Fukuoka-shi, Japan, 811-1395
Research Site
Kagoshima-shi, Japan, 892-0833
Research Site
Nagoya-shi, Japan, 464-8681
Research Site
Osaka-shi, Japan, 540-0006
Research Site
Sapporo-shi, Japan, 003-0804
Research Site
Shinagawa-ku, Japan, 142-8666
Research Site
Suita-shi, Japan, 565-0871
Korea, Republic of
Research Site
Cheongju-si, Korea, Republic of, 28644
Research Site
Daegu, Korea, Republic of, 41404
Research Site
Incheon, Korea, Republic of, 21565
Research Site
Seongnam-si, Korea, Republic of, 13620
Research Site
Seoul, Korea, Republic of, 03080
Research Site
Seoul, Korea, Republic of, 03722
Research Site
Seoul, Korea, Republic of, 135-710
Research Site
Seoul, Korea, Republic of, 158-710
Mexico
Research Site
Estado de México, Mexico, 50080
Research Site
Merida, Mexico, 97000
Research Site
Merida, Mexico, 97133
Research Site
Mexico, Mexico, 6760
Research Site
Mérida, Mexico, 97070
Research Site
San Juan del Rio, Mexico, 76800
Peru
Research Site
Cusco, Peru, CUSCO 01
Research Site
Lima, Peru, LIMA 01
Research Site
Lima, Peru, Lima 18
Research Site
Lima, Peru, LIMA 27
Research Site
Lima, Peru, LIMA 34
Research Site
Lima, Peru, LIMA 41
Research Site
San Borja, Peru, LIMA 41
Poland
Research Site
Elbląg, Poland, 82-300
Research Site
Gdańsk, Poland, 80-952
Research Site
Grzepnica, Poland, 72-003
Research Site
Tarnobrzeg, Poland, 39-400
Research Site
Warszawa, Poland, 01-748
Research Site
Warszawa, Poland, 03-291
Research Site
Łódź, Poland, 93-513
Romania
Research Site
Bucharest, Romania, 013811
Research Site
Bucuresti, Romania, 011171
Research Site
Bucuresti, Romania, 030171
Research Site
Cluj Napoca, Romania, 400015
Research Site
Cluj-Napoca, Romania, 400015
Russian Federation
Research Site
Arkhangelsk, Russian Federation, 163045
Research Site
Ivanovo, Russian Federation, 153040
Research Site
Moscow, Russian Federation, 115478
Research Site
Omsk, Russian Federation, 644013
Research Site
Saint Petersburg, Russian Federation, 191015
Research Site
Saint Petersburg, Russian Federation, 195271
Research Site
Saint Petersburg, Russian Federation, 197022
Research Site
Saransk, Russian Federation, 430005
Research Site
St-Petersburg, Russian Federation, 197758
Research Site
St.Petersburg, Russian Federation, 191014
Research Site
Yaroslavl, Russian Federation, 150054
Spain
Research Site
Barcelona, Spain, 08003
Research Site
Córdoba, Spain, 14004
Research Site
Granada, Spain, 18014
Research Site
Madrid, Spain, 28034
Research Site
Majadahonda, Spain, 28222
Research Site
Oviedo, Spain, 33011
Research Site
Sevilla, Spain, 41013
Research Site
Valencia, Spain, 46026
Research Site
Zaragoza, Spain, 50009
Switzerland
Research Site
Bern, Switzerland, CH-3010
Research Site
Lausanne, Switzerland, CH-1011
Research Site
Zürich, Switzerland, CH-8063
Taiwan
Research Site
Kaohsiung, Taiwan, 00807
Research Site
Taichung, Taiwan, 407
Research Site
Taipei, Taiwan, 10048
Research Site
Taipei, Taiwan, 10449
Research Site
Taipei, Taiwan, 11217
Research Site
Taoyuan, Taiwan, 333
Turkey
Research Site
Adana, Turkey, 1260
Research Site
Ankara, Turkey, 06230
Research Site
Edirne, Turkey, 22030
Research Site
Gaziantep, Turkey, 27310
Research Site
Istanbul, Turkey, 34390
Research Site
Izmir, Turkey, 35100
Research Site
Kayseri, Turkey, 38039
Research Site
Konya, Turkey, 42080
Research Site
Mersin, Turkey, 33070
United Kingdom
Research Site
Aberdeen, United Kingdom, AB25 2ZN
Research Site
Colchester, United Kingdom, CO4 5JL
Research Site
Coventry, United Kingdom, CV2 2DX
Research Site
London, United Kingdom, W6 8RF
Research Site
Manchester, United Kingdom, M20 4BX
Research Site
Plymouth, United Kingdom, PL6 8DH.
Sponsors and Collaborators
AstraZeneca
Myriad Genetic Laboratories, Inc.
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Mark Robson, MD Memorial Sloan-Kettering Cancer Center, New York

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02000622     History of Changes
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: September 6, 2018
Last Verified: September 2018

Keywords provided by AstraZeneca:
Breast Cancer
Metastatic
Olaparib
BRCA
PARP inhibitor
HER2
chemotherapy

Additional relevant MeSH terms:
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