Clinical Trials /

Olaparib in gBRCA Mutated Pancreatic Cancer Whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy

NCT02184195

Description:

A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Maintenance Olaparib Monotherapy in Patients with gBRCA Mutated Metastatic Pancreatic Cancer whose Disease Has Not Progressed on First Line Platinum Based Chemotherapy

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title:Olaparib in gBRCA Mutated Pancreatic Cancer Whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy
  • Official Title:A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Maintenance Olaparib Monotherapy in Patients With gBRCA Mutated Metastatic Pancreatic Cancer Whose Disease Has Not Progressed on First Line Platinum Based Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: D081FC00001
  • SECONDARY ID: 2014-001589-85
  • NCT ID: NCT02184195

Trial Conditions

  • Germline BRCA1/2 Mutations and
  • Metastatic Adenocarcinoma of the Pancreas

Trial Interventions

DrugSynonymsArms
OlaparibOlaparib
OlaparibOlaparib
PlaceboPlacebo
PlaceboPlacebo

Trial Purpose

A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Maintenance Olaparib Monotherapy in Patients with gBRCA Mutated Metastatic Pancreatic Cancer whose Disease Has Not Progressed on First Line Platinum Based Chemotherapy

Detailed Description

Approximately 145 patients will be randomised using an Interactive Voice Response System /Interactive Web Response System (IVR/IWR system) in a 3:2 ratio (Olaparib:placebo) to the treatments as specified below:

- Olaparib tablets p.o. 300 mg twice daily

- Matching placebo tablets p.o. twice daily Eligible patients will be those patients with pancreas cancer previously treated for metastatic disease who have not progressed following completion of at least 16 weeks (can be more) of first line platinum-based chemotherapy. All patients must have a known deleterious or suspected deleterious germline BRCA mutation to be randomised; this may have been determined prior to enrolment into the study or may be assessed as part of the enrolment procedure for the study (via centrally provided MyriadIntegrated BRAC.

Patients will be randomised within 6 weeks after their last dose of chemotherapy (last dose is the day of the last infusion) and treatment started as soon as possible but no less than 4 and no more than 8 weeks of the last chemotherapy dose. At the time of starting protocol treatment, all previous chemotherapy treatment should be discontinued.

Following randomisation, patients will attend clinic visits weekly for the first 4 weeks of treatment (Days 8, 15, 22 and 29). Patients will then attend clinic visits every 4 weeks whilst on study treatment. Patients should continue to receive study treatment until objective radiological disease progression as per RECIST as assessed by the investigator and as long as in the investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria.

Once a patient has progressed the patient will be followed for second progression (PFS2) every 8 weeks and then survival until the final analysis.

Trial Arms

NameTypeDescriptionInterventions
OlaparibExperimentalOlaparib tablets po. 300 mg twice daily
  • Olaparib
  • Olaparib
    PlaceboPlacebo ComparatorPlacebo tablets twice daily
        • Placebo
        • Placebo

    Eligibility Criteria

    Key Inclusion Criteria

    - Histologically or cytologically confirmed pancreas adenocarcinoma receiving initial chemotherapy for metastatic disease and without evidence of disease progression on treatment

    - Patients with measurable disease and/or non-measurable or no evidence of disease assessed at baseline by CT (or MRI where CT is contraindicated) will be entered in this study.

    - Documented mutation in gBRCA1 or gBRCA2 that is predicted to be deleterious or suspected deleterious

    - Patients are on treatment with a first line platinum-based (cisplatin, carboplatin or oxaliplatin) regimen for metastatic pancreas cancer, have received a minimum of 16 weeks of continuous platinum treatment and have no evidence of progression based on investigator's opinion.

    - Patients who have received platinum as potentially curative treatment for a prior cancer (eg ovarian cancer) or as adjuvant/neoadjuvant treatment for pancreas cancer are eligible provided at least 12 months have elapsed between the last dose of platinum-based treatment and initiation of the platinum-based chemotherapy for metastatic pancreas cancer.

    Major Exclusion Criteria:

    - gBRCA1 and/or gBRCA2 mutations that are considered to be non detrimental (eg, "Variants of uncertain clinical significance" or "Variant of unknown significance" or "Variant, favour polymorphism" or "benign polymorphism" etc.)

    - Progression of tumour between start of first line platinum based chemotherapy for metastatic pancreas cancer and randomisation.

    - Cytotoxic chemotherapy or non-hormonal targeted therapy within 28 days of Cycle

    1 Day 1 is not permitted.

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

    - Any previous treatment with a PARP inhibitor, including Olaparib

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

    Primary Outcome Measures

    Measure:Progression free survival (PFS) by central review of modified RECIST 1.1
    Time Frame:Up to 4 years
    Safety Issue:No
    Description:Efficacy by assessment of PFS (time from randomisation to objective disease progression according to modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) or death) of olaparib maintenance monotherapy compared to placebo, using blinded independent central review (BICR) of radiological scans.

    Secondary Outcome Measures

    Measure:Overall survival (OS)
    Time Frame:Up to 4 years
    Safety Issue:No
    Description:Efficacy by assessment of OS (time from randomisation to death by any cause) of olaparib maintenance monotherapy compared to placebo
    Measure:Time from randomisation to second progression or death (PFS2)
    Time Frame:Up to 4 years
    Safety Issue:No
    Description:Efficacy by assessment of PFS2 (time from randomisation to second progression, defined as objective radiological or symptomatic progression, or death) of olaparib maintenance monotherapy compared to placebo.
    Measure:Time from randomisation to first subsequent therapy or death (TFST)
    Time Frame:Up to 4 years
    Safety Issue:No
    Description:Efficacy by assessment of TFST (time from randomisation to the earlier of first subsequent therapy following study treatment discontinuation, or death) of olaparib maintenance monotherapy compared to placebo.
    Measure:Time from randomisation to second subsequent therapy or death (TSST)
    Time Frame:Up to 4 years
    Safety Issue:No
    Description:Efficacy by assessment of TSST (time from randomisation to the earlier of second subsequent therapy following study treatment discontinuation, or death) of olaparib maintenance monotherapy compared to placebo.
    Measure:Time from randomisation to study treatment discontinuation or death (TDT)
    Time Frame:Up to 4 years
    Safety Issue:No
    Description:Efficacy by assessment of TDT (time from randomisation to the earlier of study treatment discontinuation or death) of olaparib maintenance monotherapy compared to placebo. compared to placebo.
    Measure:Objective response rate by BICR using modified RECIST 1.1
    Time Frame:Up to 4 years.
    Safety Issue:No
    Description:Efficacy by assessment of objective response rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo
    Measure:Disease control rate by BICR using modified RECIST 1.1
    Time Frame:Up to 4 years
    Safety Issue:No
    Description:Efficacy by assessment of disease control rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo.
    Measure:Adjusted mean change from baseline in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire
    Time Frame:Up to 4 years
    Safety Issue:No
    Description:Assessment of the effect of olaparib on health-related quality of life (QoL) as measured by the EORTC-QLQ-C30 global QoL scale
    Measure:Safety and tolerability of olaparib
    Time Frame:Up to 4 years
    Safety Issue:Yes
    Description:Assessment of adverse events (AEs), physical examination, vital signs including blood pressure (BP), pulse, electrocardiogram (ECG) and laboratory findings including clinical chemistry and haematology.
    Measure:Improvement rate of global quality of life (QoL)
    Time Frame:Up to 4 years
    Safety Issue:No
    Description:Assessment of the effect of olaparib on improvement rate of global health status/QoL and pancreatic pain as measured by the EORTC-QLQ-C30 global QoL scale and the PAN-26 pancreatic pain scale.

    Trial Keywords

    • BRCA, metastatic adenocarcinoma pancreas, maintenance olaparib monotherapy, first line platinum chemotherapy, pancreatic cancer, PARP inhibitor