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

URL:

https://clinicaltrials.gov/show/NCT02282020

Trial Eligibility

Document

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

  • ORG STUDY ID: D0816C00010
  • NCT ID: NCT02282020

Conditions

  • Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity

Interventions

DrugSynonymsArms
OLAPARIB1/OLAPARIB
Single agent chemotherapy2/CHEMOTHERAPY

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. Patients are eligible to
      undergo BRCA testing even if they have not yet had recurrence or progression of disease >6
      months (>/=183 days) after completion of their last platinum therapy.

Trial Arms

NameTypeDescriptionInterventions
1/OLAPARIBExperimentalolaparib 300mg oral tablets; twice daily
  • OLAPARIB
2/CHEMOTHERAPYActive ComparatorPhysician'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. Patients are eligible to undergo BRCA testing even if they have not yet had
             recurrence or progression of disease >6 months (>/=183 days) after completion of their
             last platinum therapy.

          -  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).
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Maximum of 45 Months
Safety Issue:
Description:Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used by a Blinded Independent Central Review (BICR) to assess participant response to treatment Objective Response Rate (ORR) is the number of participants with Complete Response (CR) or Partial Response (PR) in the Measurable Disease Analysis Set (MDAS). Complete response is declared when all lesions have disappeared or all lesions have disappeared and all nodal disease is < 10 mm each. Partial response is declared when there is a decrease in sum of diameters of target lesions ≥ 30%.

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:Maximum of 45 Months
Safety Issue:
Description:RECIST 1.1 criteria was used to assess participant response to treatment. PFS was defined as the time from randomization until the date of objective radiological disease progression according to RECIST 1.1 or death (by any cause in the absence of disease progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to disease progression (i.e., date of RECIST progression/death or censoring - date of randomization +1).
Measure:Time From Randomisation to Second Progression (PFS2)
Time Frame:Maximum of 45 Months
Safety Issue:
Description:Time from randomization to PFS2 was defined as the time from the date of randomization to the earliest of the progression events subsequent to first progression or death. The date of second progression was recorded by the investigator and defined according to local standard clinical practice, and could involve objective radiological, clinical, cancer antigen-125 (CA-125) progression or death. CA-125 progression was assessed per Gynecological Cancer Intergroup (GCIG) criteria.
Measure:Overall Survival (OS)
Time Frame:Maximum of 45 Months
Safety Issue:
Description:
Measure:Time To Earliest Progression By RECIST 1.1 Or Cancer Antigen (CA) -125 Or Death
Time Frame:Maximum of 45 Months
Safety Issue:
Description:Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used to assess participant response to treatment. CA-125 progression was assessed per Gynecological Cancer Intergroup (GCIG).
Measure:Time From Randomization To First Subsequent Therapy Or Death (TFST)
Time Frame:Maximum of 45 Months
Safety Issue:
Description:TFST was defined as the time from the date of randomization to the earlier of first subsequent therapy start date or death.
Measure:Time From Randomization To Second Subsequent Therapy Or Death (TSST)
Time Frame:Maximum of 45 Months
Safety Issue:
Description:TSST was defined as the time from the date of randomization to the earlier of second subsequent chemotherapy start date following study treatment discontinuation, or death.
Measure:Time From Randomization To Study Treatment Discontinuation Or Death (TDT)
Time Frame:Maximum of 45 Months
Safety Issue:
Description:TDT was defined as the time from randomization to the earlier of the date of study treatment discontinuation or death.
Measure:Duration of Response (DoR)
Time Frame:Maximum of 45 Months
Safety Issue:
Description:Duration of response is the time from the first documentation of complete response (CR) or partial response (PR) until the date of progression or death, or the last evaluable RECIST assessment for participants that do not progress or progress after 2 missed assessments. Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used to assess participant response to treatment.
Measure:Time to Response (TTR)
Time Frame:Maximum of 45 Months
Safety Issue:
Description:TTR was defined as the time from randomization until the date of first documented response by Blinded independent central review (BICR) assessment.
Measure:Mean Change From Baseline In Trial Outcome Index (TOI) Score
Time Frame:Baseline (Day 1) to Week 48 (±1 week)
Safety Issue:
Description:The TOI score was derived from the sum of the scores of the 25 items included in the physical well-being (7 items), functional well-being (7 items), and additional concerns ovarian cancer subscale (11 items) of the FACT-O questionnaire Version 4. A negative change in score from baseline indicated a worsening in symptoms.
Measure:Number of Participants Who Show an Improvement in TOI Score
Time Frame:Baseline (Day 1) to Week 48 (±1 week)
Safety Issue:
Description:The TOI score was derived from the sum of the scores of the 25 items included in the physical well-being (7 items), functional well-being (7 items), and additional concerns ovarian cancer subscale (11 items) of the FACT-O questionnaire Version 4. TOI score ranges from 0 to 100, a higher score indicates a higher health-related quality of life (HRQoL). A change in at least 10 points was considered clinically relevant.
Measure:Objective Response Rate (ORR) in Breast Cancer Susceptibility (BRCA) Gene Population by Blinded Independent Central Review (BICR)
Time Frame:Maximum of 45 Months
Safety Issue:
Description:BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis). The number of participants with complete or partial response per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. Partial response is declared when there is a decrease in sum of target disease ≥ 30%. Complete response is declared when all lesions have disappeared or all lesions have disappeared and all nodal disease is < 10 mm each.
Measure:Number of Participants Who Experienced Disease Progression or Death in BRCA Gene Population by Blinded Independent Central Review (BICR)
Time Frame:Maximum of 45 Months
Safety Issue:
Description:BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis). Progressive disease was defined as at least 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Measure:Number of Participants Who Experienced Second Progression or Death (PFS2) in BRCA Gene Population
Time Frame:Maximum of 45 Months
Safety Issue:
Description:BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis).
Measure:Overall Survival (OS) in BRCA Gene Population
Time Frame:Maximum of 45 Months
Safety Issue:
Description:BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis). OS in BRCA gene population was measured by the number of participants who died due to any cause.
Measure:Number of Participants Who Discontinued Study Treatment or Died in BRCA Gene Population
Time Frame:Maximum of 45 Months
Safety Issue:
Description:BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis).
Measure:Number of Participants Who Received Subsequent Chemotherapy or Died in BRCA Gene Population
Time Frame:Maximum of 45 Months
Safety Issue:
Description:BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis).
Measure:Number of Participants Who Received Second Subsequent Chemotherapy or Died in BRCA Gene Population
Time Frame:Maximum of 45 Months
Safety Issue:
Description:BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis).
Measure:Geometric Mean Plasma Concentration of Olaparib
Time Frame:Day 1, 1 hour post-dose and Day 29 pre-dose
Safety Issue:
Description:
Measure:Number of Participants Who Experience at Least One Adverse Event (AE)
Time Frame:Maximum of 45 Months
Safety Issue:
Description:An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.

Details

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

Trial Keywords

  • BRCA, ovarian, platinum, chemotherapy,

Last Updated

August 12, 2021