Clinical Trials /

Olaparib Treatment in Relapsed Germline Breast Cancer Susceptibility Gene (BRCA) Mutated Ovarian Cancer Patients Who Have Progressed at Least 6 Months After Last Platinum Treatment and Have Received at Least 2 Prior Platinum Treatments

NCT02282020

Description:

Comparison of olaparib vs. physician's choice of single agent standard of care non-platinum based chemotherapy in patients with germline Breast Cancer susceptibility gene (gBRCA) mutated ovarian cancer who have progressed at least 6 months after the last platinum based chemotherapy. Patient should have received at least 2 prior lines of platinum based chemotherapy. The aim of the study is to assess the efficacy and safety of olaparib tablets.

Related Conditions:
  • Endometrial Carcinoma
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Olaparib</span> Treatment in Relapsed Germline <span class="go-doc-concept go-doc-disease">Breast Cancer</span> Susceptibility Gene (BRCA) <span class="go-doc-concept go-doc-keyword">Mutated</span> <span class="go-doc-concept go-doc-disease">Ovarian Cancer</span> Patients Who Have Progressed at Least 6 Months After Last <span class="go-doc-concept go-doc-intervention">Platinum</span> Treatment and Have Received at Least 2 Prior <span class="go-doc-concept go-doc-intervention">Platinum</span> Treatments

Title

  • Brief Title: Olaparib Treatment in Relapsed Germline Breast Cancer Susceptibility Gene (BRCA) Mutated Ovarian Cancer Patients Who Have Progressed at Least 6 Months After Last Platinum Treatment and Have Received at Least 2 Prior Platinum Treatments
  • Official Title: A Phase III, Open Label, Randomised, Controlled, Multi-centre Study to Assess the Efficacy and Safety of Olaparib Monotherapy Versus Physician's Choice Single Agent Chemotherapy in the Treatment of Platinum Sensitive Relapsed Ovarian Cancer in Patients Carrying Germline BRCA1/2 Mutations
  • Clinical Trial IDs

    NCT ID: NCT02282020

    ORG ID: D0816C00010

    Trial Conditions

    Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity

    Trial Interventions

    Drug Synonyms Arms
    OLAPARIB 1/OLAPARIB
    Single agent chemotherapy 2/CHEMOTHERAPY

    Trial Purpose

    Comparison of olaparib vs. physician's choice of single agent standard of care non-platinum
    based chemotherapy in patients with germline Breast Cancer susceptibility gene (gBRCA)
    mutated ovarian cancer who have progressed at least 6 months after the last platinum based
    chemotherapy. Patient should have received at least 2 prior lines of platinum based
    chemotherapy. The aim of the study is to assess the efficacy and safety of olaparib tablets.

    Detailed Description

    This open label, randomised, controlled, multi-centre study will assess the efficacy and
    safety of single agent olaparib vs. standard of care, based on physician's choice of single
    agent chemotherapy ( i.e paclitaxel, or topotecan, or pegylated liposomal doxorubicin, or
    gemcitabine) in platinum sensitive or partially platinum sensitive relapsed ovarian cancer
    patients who carry germline deleterious or suspected deleterious BRCA mutation and who have
    received at least 2 prior lines of platinum based chemotherapy.

    Trial Arms

    Name Type Description Interventions
    1/OLAPARIB Experimental olaparib 300mg oral tablets; twice daily OLAPARIB
    2/CHEMOTHERAPY Active Comparator Physician's choice single agent chemotherapy Single agent chemotherapy

    Eligibility Criteria

    Inclusion Criteria:

    - Patients must be 18 years of age

    - Patients with histologically diagnosed relapsed high grade serous ovarian cancer
    (including primary peritoneal and/or fallopian tube cancer) or high grade
    endometrioid cancer

    - Documented germline mutation in Breast Cancer susceptibility genes: BRCA1 and/or
    BRCA2 that is predicted to be deleterious or suspected deleterious (known or
    predicted to be detrimental/lead to loss of function)

    - At least one lesion that can be accurately assessed at baseline by CT/MRI and is
    suitable for repeated assessment.

    - Patients must have received at least 2 prior platinum based lines of chemotherapy -
    Patients must be partially platinum sensitive or platinum sensitive

    - Patients must be suitable to start treatment with single agent chemotherapy based on
    physician's choice

    - Patients must have normal organ and bone marrow function measured within 28 days of
    randomisation,

    - Eastern Cooperative Oncology Group (ECOG) performance status 0-2

    - Patients must have a life expectancy 16 weeks

    - Formalin fixed, paraffin embedded tumour sample from the primary or recurrent cancer
    must be available for central testing.

    Exclusion Criteria:

    - BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental

    - Exposure to any investigational product within 30 days or 5 half lives (whichever is
    longer) prior to randomisation

    - Any previous treatment with a Polyadenosine 5'diphosphoribose polymerisation (PARP)
    inhibitor, including olaparib.

    - Patients who have platinum resistant or refractory disease

    - Patients receiving any systemic chemotherapy within 3 weeks prior to first dose of
    study treatment

    - Previous single agent exposure to the selected chemotherapy regimen for
    randomisation. - Prior malignancy in the last 5 years, unless curatively treated and
    recurrence free (few exceptions apply).

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 96 Years

    Eligible Gender: Female

    Primary Outcome Measures

    Progression Free Survival (PFS) by blinded independent central review using Response Evaluation Criteria In Solid Tumours (RECIST) data

    Secondary Outcome Measures

    Efficacy of olaparib vs. physician's choice single agent chemotherapy by assessment of Overall Survival (OS)

    Efficacy in patients following platinum based chemotherapy by assessment of time from randomisation to second progression

    Efficacy in patients following platinum based chemotherapy by assessment of time to earliest progression by Cancer Antigen (CA-125) or death

    Time to deterioration of Health-Related Quality of Life (HRQoL) as assessed by trial outcome index (TOI) and the Functional Assessment of Cancer Therapy - Ovarian (FACT-O)

    Efficacy in patients with a deleterious or suspected deleterious variant in either of the BRCA genes by assessment of PFS.

    Efficacy of olaparib by time to first subsequent therapy or death (TFST).

    Efficacy of olaparib by time to second subsequent therapy or death (TSST).

    Efficacy of olaparib by time from randomisation to study treatment discontinuation or death (TDT).

    Safety and tolerability of olaparib by assessment of the number of Adverse Events (AEs).

    Safety and tolerability of olaparib by review of laboratory parameters, ECG and vital signs

    Efficacy in patients following platinum based chemotherapy by assessment of time to earliest progression by RECIST or death

    Trial Keywords

    BRCA, ovarian, platinum, chemotherapy,