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Trial record 1 of 1 for:    nct02032823
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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 : December 8, 2021
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 Corp.
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE January 3, 2014
First Posted Date  ICMJE January 10, 2014
Results First Submitted Date  ICMJE September 24, 2021
Results First Posted Date  ICMJE December 8, 2021
Last Update Posted Date December 8, 2021
Actual Study Start Date  ICMJE April 22, 2014
Actual Primary Completion Date March 27, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 9, 2021)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 9, 2014)
Efficacy of adjuvant treatment with olaparib on Invasive Disease Free Survival (IDFS). [ Time Frame: Patients will be followed for disease recurrence and new cancers for approximately 10 years following randomisation ]
Recurrence assessments on a 3 monthly basis during the first 2 years and on a 6 monthly basis in year 3, 4, 5 and annually from year 6 to 10. MRI performed every 12 months beginning 6 months after randomization
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 9, 2021)
  • 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
  • Overall Survival (OS) [ Time Frame: From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months) ]
    An OS event is defined as death by any cause.
  • Number of Participants With Contralateral Breast Cancers, New Primary Ovarian Cancer, New Primary Fallopian Tube Cancer and New Primary Peritoneal Cancer [ Time Frame: From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 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.
  • Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Neoadjuvant Chemotherapy [ Time Frame: 6 and 12 months after randomisation ]
    Change from baseline for FACIT-Fatigue Score at 6 and 12 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.
  • Change From Baseline for FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) Score for Participants Who Completed Adjuvant Chemotherapy [ Time Frame: 6 and 12 months after randomisation ]
    Change from baseline for FACIT-Fatigue Score at 6 and 12 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.
  • 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 and 12 months after randomisation ]
    Change from baseline for EORTC QLQ-C30 Global health status QOL (Quality of Life) Score at 6 and 12 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.
  • 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 and 12 months after randomisation ]
    Change from baseline for EORTC QLQ-C30 Global health status QOL (Quality of Life) Score at 6 and 12 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 9, 2014)
  • Efficacy of adjuvant treatment with olaparib on overall survival (OS). [ Time Frame: OS follow up will be done every 12 months following completion of 10 year new cancer/recurrence follow up. ]
  • Efficacy of adjuvant treatment with olaparib on Distant Disease Free Survival (DDFS) [ Time Frame: Physical examination will be performed at weeks 12, 24, 38, 52. In follow-up period in year 2 every 3 months, in year 3, 4,5 every 6 months and year 6 to 10 every 12 months. MRI to be performed every 12 months after the 6 months scan. ]
  • Efficacy of adjuvant treatment with olaparib on the incidence of new invasive breast primary cancer and/or new epithelial ovarian cancer. [ Time Frame: New cancer assessments will be performed at day 1, weeks 12, 24, 38, 52. In follow-up period in year 2 every 3 months, in year 3, 4,5 every 6 months and year 6 to 10 every 12 months. MRI to be performed every 12 months after the 6 months scan. ]
  • Efficacy of olaparib on patient reported outcomes using the FACIT fatigue scale and EORTC QLQ-C30 QoL scale. [ Time Frame: Baseline assessmnet prior to day 1 and then at week 24, 52 and month 18 and 24 following randomisation. ]
  • Efficacy of olaparib in patients identified as having 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). [ Time Frame: Within 15 years from last subject last visit. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Olaparib as Adjuvant Treatment in Patients With Germline BRCA Mutated High Risk HER2 Negative Primary Breast Cancer
Official Title  ICMJE 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
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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • 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
  • 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.
Study Arms  ICMJE
  • Experimental: Olaparib
    Olaparib tablets 300mg b.i.d. p.o.
    Intervention: Drug: Olaparib
  • Placebo Comparator: Placebo
    Placebo tablets b.i.d. p.o.
    Intervention: Drug: Placebo
Publications * Tutt ANJ, Garber JE, Kaufman B, Viale G, Fumagalli D, Rastogi P, Gelber RD, de Azambuja E, Fielding A, Balmaña J, Domchek SM, Gelmon KA, Hollingsworth SJ, Korde LA, Linderholm B, Bandos H, Senkus E, Suga JM, Shao Z, Pippas AW, Nowecki Z, Huzarski T, Ganz PA, Lucas PC, Baker N, Loibl S, McConnell R, Piccart M, Schmutzler R, Steger GG, Costantino JP, Arahmani A, Wolmark N, McFadden E, Karantza V, Lakhani SR, Yothers G, Campbell C, Geyer CE Jr; OlympiA Clinical Trial Steering Committee and Investigators. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med. 2021 Jun 24;384(25):2394-2405. doi: 10.1056/NEJMoa2105215. Epub 2021 Jun 3.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 31, 2020)
1836
Original Estimated Enrollment  ICMJE
 (submitted: January 9, 2014)
1320
Estimated Study Completion Date  ICMJE May 28, 2029
Actual Primary Completion Date March 27, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Canada,   China,   France,   Germany,   Hungary,   Iceland,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Poland,   Portugal,   Puerto Rico,   Spain,   Sweden,   Switzerland,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02032823
Other Study ID Numbers  ICMJE D081CC00006
NSABP B-55 ( Other Identifier: NSABP )
BIG 6-13 ( Other Identifier: Breast International Group )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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
Supporting Materials: 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
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE
  • 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 Corp.
Investigators  ICMJE
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
PRS Account AstraZeneca
Verification Date November 2021

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