This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Olaparib as Adjuvant Treatment in Patients With Germline BRCA Mutated High Risk HER2 Negative Primary Breast Cancer (OlympiA)

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: NCT02032823
Recruitment Status : Active, not recruiting
First Posted : January 10, 2014
Results First Posted : December 8, 2021
Last Update Posted : January 29, 2024
Sponsor:
Collaborators:
Breast International Group
Frontier Science & Technology Research Foundation, Inc.
NRG Oncology
Myriad Genetic Laboratories, Inc.
Br.E.A.S.T. -Data Center & Operational Office Institut Jules Bordet
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
AstraZeneca

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
Olaparib treatment in patients with germline BRCA1/2 mutations and high risk HER2 negative primary breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Olaparib Drug: Placebo Phase 3

Detailed Description:

Patients will be randomised in 1:1 ratio to either olaparib or placebo. Randomisation will be stratified by Hormone receptor status (ER and/or PgR positive/HER2 negative versus TNBC), prior neoadjuvant versus adjuvant chemotherapy and prior platinum use for breast cancer.

Randomised patients will receive study treatment for up to a maximum of 12 months. All patients will have safety assessments every 2 weeks during the first month, every 4 weeks for the following 5 months and 3 monthly for the remaining 6 months of study treatment plus 30 days after its discontinuation. Following randomisation, all patients will be assessed regularly for signs, symptoms and evidence of disease recurrence by taking medical history, physical examination and mammogram/breast MRI. Efficacy assessments will be performed on a 3 monthly basis during the first 2 years, followed by 6 monthly assessments for years 3, 4 and 5 and annually thereafter. All patients (except those with bilateral mastectomy) will have mammogram / breast MRI annually for 10 years beginning 6 months after randomisation.

All randomised patients will have clinical assessment visits for 10 years following their randomisation into the study. Once a patient completes 10 years of clinical assessment they will enter the survival follow up phase of the trial which will continue until 10 years after the last patient is randomised.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1836 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Parallel Group, Placebo-controlled Multi-centre Phase III Study to Assess the Efficacy and Safety of Olaparib Versus Placebo as Adjuvant Treatment in Patients With gBRCA1/2 Mutations and High Risk HER2 Negative Primary Breast Cancer Who Have Completed Definitive Local Treatment and Neoadjuvant or Adjuvant Chemotherapy
Actual Study Start Date : April 22, 2014
Actual Primary Completion Date : March 27, 2020
Estimated Study Completion Date : May 28, 2029

Resource links provided by the National Library of Medicine

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

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Olaparib
Olaparib tablets 300mg b.i.d. p.o.
 Drug: Olaparib
Patients will be administred olaparib orally twice daily (b.i.d.) 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.
Other Name: Lynparza
Placebo Comparator: Placebo
Placebo tablets b.i.d. p.o.
 Drug: Placebo
Patients will be administred matching placebo. Two (2) 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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Invasive Disease Free Survival (IDFS) [ Time Frame: From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months) ]
    An IDFS event is defined as the first occurrence of loco-regional or distant recurrence or new cancer or death from any cause.


Secondary Outcome Measures :
  1. Distant Disease Free Survival (DDFS) [ Time Frame: From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months) ]
    A DDFS event is defined as documented evidence of first distant recurrence of breast cancer or death from any cause

  2. Overall Survival (OS) [ Time Frame: From date of randomisation to data cut off: 12 July 2021 (approximately 7 years 3 months) ]
    An OS event is defined as death by any cause.

  3. Number of Participants With Contralateral Invasive and Non-invasive Breast Cancer, New Primary Ovarian Cancer, New Primary Fallopian Tube Cancer and New Primary Peritoneal Cancer [ Time Frame: From date of randomisation to data cut off: 12 July 2021 (approximately 7 years 3 months) ]
    Number of patients with contralateral invasive breast cancer, contralateral non-invasive breast cancer, new primary ovarian cancer, new primary fallopian tube cancer and new primary peritoneal cancer. Analysis of contralateral breast cancers exclude patients with a bilateral mastectomy prior to randomisation. Analysis of new primary ovarian cancers excludes male patients and patients with a bilateral oophorectomy prior to randomisation. Analysis of new primary fallopian tube cancer excludes male patients and patients with a bilateral salpingectomy prior to randomisation. Analysis of new primary peritoneal cancers excludes male patients.

  4. Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Neoadjuvant Chemotherapy [ Time Frame: 6, 12, 18 and 24 months after randomisation (data cut off: 12 July 2021) ]
    Change from baseline for FACIT-Fatigue Score at 6, 12, 18 and 24 months for patients who completed neoadjuvant chemotherapy. Adjusted least-square mean changes and 95% Confidence Interval (CI) are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. FACIT-Fatigue score ranges from 0 to 52 with higher score indicating less fatigue.

  5. Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Adjuvant Chemotherapy [ Time Frame: 6, 12, 18 and 24 months after randomisation (data cut off: 12 July 2021) ]
    Change from baseline for FACIT-Fatigue Score at 6, 12, 18 and 24 months for patients who completed adjuvant chemotherapy. Adjusted least-square mean changes and 95% CI are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. FACIT-Fatigue score ranges from 0 to 52 with higher score indicating less fatigue.

  6. Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Neoadjuvant Chemotherapy [ Time Frame: 6, 12, 18 and 24 months after randomisation (data cut off: 12 July 2021) ]
    Change from baseline for EORTC QLQ-C30 Global health status QOL (Quality of Life) Score at 6, 12, 18 and 24 months for patients who completed neoadjuvant chemotherapy. Adjusted least-square mean changes and 95% CI are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. EORTC QLQ-C30 scores range from 0 to 100 with higher score indicating better quality of life.

  7. Change From Baseline for EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questions 30) Scores for Participants Who Completed Adjuvant Chemotherapy [ Time Frame: 6, 12, 18 and 24 months after randomisation (data cut off: 12 July 2021) ]
    Change from baseline for EORTC QLQ-C30 Global health status QOL (Quality of Life) Score at 6, 12, 18 and 24 months for patients who completed adjuvant chemotherapy. Adjusted least-square mean changes and 95% CI are obtained from mixed model for repeated measures (MMRM) analysis of the change from baseline. Only patients with evaluable baseline forms are included. EORTC QLQ-C30 scores range from 0 to 100 with higher score indicating better quality of life.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast that is one of the following phenotypes:

    1. Triple negative breast cancer defined as: ER and PgR negative AND HER2 negative (not eligible for anti-HER2 therapy)
    2. ER and/or PgR positive, HER2 negative
  • Documented germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function).
  • Completed adequate breast and axilla surgery.
  • Completed at least 6 cycles neoadjuvant or adjuvant chemotherapy containing anthracyclines, taxanes or the combination of both. Prior platinum as potentially curative treatment for prior cancer (e.g. ovarian) or as adjuvant or neoadjuvant treatment for breast cancer is allowed.
  • ECOG 0-1.

Exclusion criteria:

  • Any previous treatment with a PARP inhibitor, including olaparib and/or known hypersensitivity to any of the excipients of study treatment.

  • Patients with second primary malignancy. EXCEPTIONS are:

    1. adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, Ductal Carcinoma in situ (DCIS) of the breast, stage 1 grade 1 endometrial carcinoma
    2. other solid tumours and lymphomas (without bone marrow involvement) diagnosed ≥ 5 years prior to randomisation and treated with no evidence of disease recurrence and for whom no more than one line of chemotherapy was applied.
  • Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks. Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
  • Evidence of metastatic breast cancer
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT02032823


Locations
Show Show 699 study locations
Sponsors and Collaborators
AstraZeneca
Breast International Group
Frontier Science & Technology Research Foundation, Inc.
NRG Oncology
Myriad Genetic Laboratories, Inc.
Br.E.A.S.T. -Data Center & Operational Office Institut Jules Bordet
Merck Sharp & Dohme LLC
Investigators
Layout table for investigator information
Principal Investigator: Andrew Tutt, Doctor of Medicine Integrated Cancer Centre Guy's Hospital, King's College, London School of Medicine, London, UK
Principal Investigator: Judy Garber, Doctor of Medicine Harvard Medical School, Center for Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Susan F. Smither Center for Women's Cancers, 450 Brookline Avenue, Boston; MA 02215, US
Principal Investigator: Charles Geyer, Doctor of Medicine Virginia Commonwealth University Massey Cancer Center, McGlothlin Medical Education Center, Room 12-217, 1201 East Marshall St., PO Box 980070, Richmond, VA 23298-0070, USA
  Study Documents (Full-Text)

Documents provided by AstraZeneca:
Study Protocol and Statistical Analysis Plan  [PDF] May 6, 2021

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

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

Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02032823    
Other Study ID Numbers: D081CC00006
NSABP B-55 ( Other Identifier: NSABP )
BIG 6-13 ( Other Identifier: Breast International Group )
2013-003839-30 ( EudraCT Number )
First Posted: January 10, 2014    Key Record Dates
Results First Posted: December 8, 2021
Last Update Posted: January 29, 2024
Last Verified: January 2024
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.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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
Adjuvant
Olaparib
BRCA 1/2
HER2
Additional relevant MeSH terms:
Layout table for 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