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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by AstraZeneca
Sponsor:
Collaborators:
Breast International Group
Frontier Science & Technology Research Foundation, Inc.
NRG Oncology
Myriad Genetics - BRACAnalysis test for FDA Premarket Approval (PMA)
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02032823
First received: January 3, 2014
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

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 Intervention Phase
Breast Cancer
Drug: Olaparib
Drug: Placebo
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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. MRI performed every 12 months beginning 6 months after randomization


Secondary Outcome Measures:
  • 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. ] [ 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. 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. 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 ]

Estimated Enrollment: 7600
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)
Arms Assigned Interventions
Experimental: Olaparib
Tablet orally - twice daily, the tablets: 150 mg and 100 mg
Drug: Olaparib
Tablet orally - twice daily, the tablets: 150 mg and 100 mg
Placebo Comparator: Placebo
Tablet orally - twice daily, the tablets: 150 mg and 100 mg
Drug: Placebo
Tablet orally - twice daily, the tablets: 150 mg and 100 mg

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed non-metastatic primary triple negative invasive adenocarcinoma of the breast.
  • Invasive Triple Negative Breast Cancer
  • Documented 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 cancer, EXCEPTIONS: 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, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥ 5 years prior to randomization. More than one course of chemotherapy for previous malignancies.
  • Resting ECG with QTc > 470 msec detected on 2 or more time points within a 24 hour period or family history of long QT syndrome. If ECG demonstrates QTc >470 msec, patient will be eligible only if repeat ECG demonstrates QTc ≤470 msec.
  • Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
  • Whole blood transfusions in the last 120 days prior to entry to the study which may interfere with gBRCA testing
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02032823

Contacts
Contact: Carsten Goessl, Dr + 1 301 398 0314 ClinicalTrialTransparency@astrazeneca.com

  Show 187 Study Locations
Sponsors and Collaborators
AstraZeneca
Breast International Group
Frontier Science & Technology Research Foundation, Inc.
NRG Oncology
Myriad Genetics - BRACAnalysis test for FDA Premarket Approval (PMA)
Investigators
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
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02032823     History of Changes
Other Study ID Numbers: D081CC00006, BIG 6-13, NSABP B-55
Study First Received: January 3, 2014
Last Updated: September 2, 2014
Health Authority: United States: Food and Drug Administration
China: Food and Drug Administration
China: Ethics Committee
Japan: Ministry of Health, Labor and Welfare
European Union: European Medicines Agency

Keywords provided by AstraZeneca:
Breast Cancer
Adjuvant
Olaparib
BRCA 1/2
HER2

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on September 30, 2014