Clinical Trials /

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

NCT02032823

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: D081CC00006
  • SECONDARY ID: NSABP B-55
  • SECONDARY ID: BIG 6-13
  • NCT ID: NCT02032823

Trial Conditions

  • Breast Cancer

Trial Interventions

DrugSynonymsArms
OlaparibLynparzaOlaparib
PlaceboPlacebo

Trial 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

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.

Trial Arms

NameTypeDescriptionInterventions
OlaparibExperimentalOlaparib tablets 300mg b.i.d. p.o.
  • Olaparib
    PlaceboPlacebo ComparatorPlacebo tablets b.i.d. p.o.
      • Placebo

    Eligibility 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

    Maximum Eligible Age:130 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:Both
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Invasive Disease Free Survival (IDFS)
    Time Frame:Up to 10 years
    Safety Issue:No
    Description: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

    Measure:Overall survival (OS)
    Time Frame:Until 10 years after the last patient is randomised
    Safety Issue:No
    Description:Efficacy by assessment of OS (time from randomisation to death by any cause).
    Measure:Distant Disease Free Survival (DDFS)
    Time Frame:Up to 10 years
    Safety Issue:No
    Description:Time from randomisation until documented evidence of first distant recurrence of breast cancer
    Measure: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
    Safety Issue:No
    Description: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
    Measure: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
    Safety Issue:No
    Description:Retrospective analysis of samples
    Measure:Exposure to Olaparib (in plasma) in patients receiving Olaparib as adjuvant therapy
    Time Frame:Visit 4, day 29
    Safety Issue:No
    Description:Pharmacokinetic analysis
    Measure:FACIT-Fatiure symptoms and EORTC QLQ-C30 Questionnaires
    Time Frame:Up to 2 years
    Safety Issue:No
    Description:Assess weather olaparib arm patients may experience greater fatigue (FACIT-Fatigue), greater GI symptoms and no difference in Quality of Life (EORTC QLQ-C30)

    Trial Keywords

    • Breast Cancer
    • Adjuvant
    • Olaparib
    • BRCA 1/2
    • HER2