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

• Register: ClinicalTrials.gov
• Last refreshed on: 5 February 2024
• Main ID: NCT02032823
• Date of registration: 03/01/2014
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: Olaparib as Adjuvant Treatment in Patients With Germline BRCA Mutated High Risk HER2 Negative Primary Breast Cancer OlympiA
• Scientific 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
• Date of first enrolment: April 22, 2014
• Target sample size: 1836
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02032823
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 3

Countries of recruitment

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

Contacts

• Name: Charles Geyer, Doctor of Medicine
• Affiliation: 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

• Name: Judy Garber, Doctor of Medicine
• Affiliation: 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

• Name: Andrew Tutt, Doctor of Medicine
• Affiliation: Integrated Cancer Centre Guy's Hospital, King's College, London School of Medicine, London, UK

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 130 Years
Gender: All

Health Condition(s) or Problem(s) studied

Breast Cancer

Intervention(s)

Drug: Olaparib

Drug: Placebo

Primary Outcome(s)

Invasive Disease Free Survival (IDFS) [Time Frame: From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months)]

Secondary Outcome(s)

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)]

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)]

Distant Disease Free Survival (DDFS) [Time Frame: From date of randomisation to data cut off: 27 March 2020 (approximately 5 years 11 months)]

Overall Survival (OS) [Time Frame: From date of randomisation to data cut off: 12 July 2021 (approximately 7 years 3 months)]

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 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 (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)]

Secondary ID(s)

D081CC00006

2013-003839-30

BIG 6-13

NSABP B-55

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Myriad Genetic Laboratories, Inc.

Frontier Science & Technology Research Foundation, Inc.

NRG Oncology

Br.E.A.S.T. -Data Center & Operational Office Institut Jules Bordet

Breast International Group

Merck Sharp & Dohme LLC

Results

• Results available: Yes
• Date Posted: 08/12/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02032823