Trial record 2 of 22 for:    brca | Open Studies | United States, Massachusetts

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 January 2016 by AstraZeneca
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
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02032823
First received: January 3, 2014
Last updated: January 27, 2016
Last verified: January 2016
  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 gBRCA1/2 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:
  • Invasive Disease Free Survival (IDFS) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Time from randomisation to date of first treatment failure that is loco-regional or distant recurrence or new cancer or death from any cause


Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: Until 10 years after the last patient is randomised ] [ Designated as safety issue: No ]
    Efficacy by assessment of OS (time from randomisation to death by any cause).

  • Distant Disease Free Survival (DDFS) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Retrospective analysis of samples

  • Exposure to Olaparib (in plasma) in patients receiving Olaparib as adjuvant therapy [ Time Frame: Visit 4, day 29 ] [ Designated as safety issue: No ]
    Pharmacokinetic analysis

  • FACIT-Fatiure symptoms and EORTC QLQ-C30 Questionnaires [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Assess weather olaparib arm patients may experience greater fatigue (FACIT-Fatigue), greater GI symptoms and no difference in Quality of Life (EORTC QLQ-C30)


Other Outcome Measures:
  • Safety and tolerability of olaparib [ Time Frame: 12 months of study treatment + 30 days after treatment discontinuation ] [ Designated as safety issue: Yes ]
    Assessment of Adverse Events (AE), physical examination, vital signs including blood pressure (BP), pulse, and laboratory findings including clinical chemistry and haematology


Estimated Enrollment: 1500
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
Olaparib tablets 300mg b.i.d. p.o.
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
Placebo Comparator: Placebo
Placebo tablets b.i.d. p.o.
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 130 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 potent CYP3A inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir
  • Evidence of metastatic breast cancer
  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: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: For information regarding US sites contact NRG Oncology Clinical Coordinating Department 1-800-477-7227

  Show 797 Study Locations
Sponsors and Collaborators
AstraZeneca
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
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  NSABP B-55  BIG 6-13 
Study First Received: January 3, 2014
Last Updated: January 27, 2016
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
Israel: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Australia: Department of Health and Ageing Therapeutic Goods Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Belgium: Federal Agency for Medicines and Health Products, FAMHP
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Iceland: Icelandic Medicines Control Agency
Israel: The Israel National Institute for Health Policy Research and Health Services Research
Italy: The Italian Medicines Agency
South Korea: Korea Food and Drug Administration (KFDA)
Netherlands: ZonMw, Netherlands Organisation for Health Research and Development
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Federal Office of Public Health
Taiwan : Food and Drug Administration
Canada: Public Health Agency of Canada
Portugal: INFARMED, National Authority of Medicines and Health Products, IP

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

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

ClinicalTrials.gov processed this record on February 11, 2016