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

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
OlaparibLynparzaOlaparib
PlaceboPlacebo

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 strong CYP3A inhibitors (e.g., itraconazole, telithromycin,
             clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
             saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g.,
             ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout
             period prior to starting study treatment is 2 weeks. Concomitant use of known strong
             (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine,
             carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g.,
             bosentan, efavirenz, modafinil). The required washout period prior to starting study
             treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.

          -  Evidence of metastatic breast cancer
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Invasive Disease Free Survival (IDFS)
Time Frame:Up to 10 years
Safety Issue:
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:
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:
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:
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:
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:
Description:Pharmacokinetic analysis
Measure:FACIT-Fatiure symptoms and EORTC QLQ-C30 Questionnaires
Time Frame:Up to 2 years
Safety Issue:
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)

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

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

Last Updated

June 22, 2021