Olaparib as Adjuvant Treatment in Patients With Germline BRCA Mutated High Risk HER2 Negative Primary Breast Cancer (OlympiA)
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator
Primary Purpose: Prevention
|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|
- Invasive Disease Free Survival (IDFS) [ Time Frame: Up to 10 years ]Time from randomisation to date of first treatment failure that is loco-regional or distant recurrence or new cancer or death from any cause
- Overall survival (OS) [ Time Frame: Until 10 years after the last patient is randomised ]Efficacy by assessment of OS (time from randomisation to death by any cause).
- Distant Disease Free Survival (DDFS) [ Time Frame: Up to 10 years ]Time from randomisation until documented evidence of first distant recurrence of breast cancer
- Effect on the incidence of new primary contralateral breast cancers, new primary ovarian cancer, new primary fallopian tube cancer and new primary peritoneal cancer [ Time Frame: Up to 10 years ]Time from randomisation until documented incidence of new primary contralateral breast cancers, new primary ovarian cancer, new primary fallopian tube cancer and new primary peritoneal cancer
- Effect 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. [ Time Frame: Up to LSLV & 15 years thereafter ]Retrospective analysis of samples
- Exposure to Olaparib (in plasma) in patients receiving Olaparib as adjuvant therapy [ Time Frame: Visit 4, day 29 ]Pharmacokinetic analysis
- FACIT-Fatiure symptoms and EORTC QLQ-C30 Questionnaires [ Time Frame: Up to 2 years ]Assess weather olaparib arm patients may experience greater fatigue (FACIT-Fatigue), greater GI symptoms and no difference in Quality of Life (EORTC QLQ-C30)
- Safety and tolerability of olaparib [ Time Frame: 12 months of study treatment + 30 days after treatment discontinuation ]Assessment of Adverse Events (AE), physical examination, vital signs including blood pressure (BP), pulse, and laboratory findings including clinical chemistry and haematology
|Actual Study Start Date:||April 22, 2014|
|Estimated Study Completion Date:||February 28, 2028|
|Estimated Primary Completion Date:||March 2, 2020 (Final data collection date for primary outcome measure)|
Olaparib tablets 300mg b.i.d. p.o.
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.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02032823
|Contact: AstraZeneca Clinical Study Information Centeremail@example.com|
|Contact: For information regarding US sites contact NRG Oncology Clinical Coordinating Department 1-800-477-7227|
Show 1004 Study Locations
|Principal Investigator:||Andrew Tutt, Doctor of Medicine||Integrated Cancer Centre Guy's Hospital, King's College, London School of Medicine, London, UK|
|Principal Investigator:||Bella Kaufman, Doctor of Medicine||Sheba Medical Center, Breast Cancer Unit, 52621 Tel Hashomer, Israel|
|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|