Olaparib as Adjuvant Treatment in Patients With Germline BRCA Mutated High Risk HER2 Negative Primary Breast Cancer (OlympiA)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 Germline BRCA1/2 Mutations and High Risk HER2 Negative Primary Breast Cancer Who Have Completed Definitive Local Treatment and Neoadjuvant or Adjuvant Chemotherapy|
- 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 ] [ Designated as safety issue: No ]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. Mammogram/breast MRI performed every 12 months beginning 6 months after randomization
- Efficacy of adjuvant treatment with olaparib on overall survival (OS). [ Time Frame: Overall Survival (OS) follow up will be done every 12 months following completion of 10 year new cancer/recurrence follow up. ] [ Designated as safety issue: Yes ]
- 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. Mammogram/ breast MRI to be performed every 12 months after the 6 months scan. ] [ Designated as safety issue: No ]
- 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. Mammogram/MRI to be performed every 12 months after the 6 months scan. ] [ Designated as safety issue: No ]
- 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. ] [ Designated as safety issue: No ]
- 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. ] [ Designated as safety issue: No ]
|Study Start Date:||April 2014|
|Estimated Study Completion Date:||February 2028|
|Estimated Primary Completion Date:||March 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.
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 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 Centerfirstname.lastname@example.org|
|Contact: For information regarding US sites contact NRG Oncology Clinical Coordinating Department 1-800-477-7227|
Show 792 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|