Clinical Trials /

Efficacy and Safety of PARPi to Treat Pancreatic Cancer

NCT02511223

Description:

This is an open label, single arm, phase II trial of Olaparib for PDAC patients with BRCAness. All study subjects will receive Olaparib in a dose of 300 mg p.o twice daily. Treatment will continue until progression, intolerable toxicity or as per patient preference. Primary objective: To determine the efficacy of Olaparib monotherapy in stage IV pancreatic ductal adenocarcinoma (PDAC)with BRCAness (BRCA-Breast Cancer susceptibility gene).

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Unknown status

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Efficacy and Safety of PARPi to Treat Pancreatic Cancer
  • Official Title: PHASE II Study - EFFICACY AND SAFETY OF PARPi TO TREAT PANCREATIC CANCER

Clinical Trial IDs

  • ORG STUDY ID: SHEBA-14-2358-TG-CTIL
  • NCT ID: NCT02511223

Conditions

  • Pancreatic Cancer

Interventions

DrugSynonymsArms
OLAPARIBPARPiSingle Arm

Purpose

This is an open label, single arm, phase II trial of Olaparib for PDAC patients with BRCAness. All study subjects will receive Olaparib in a dose of 300 mg p.o twice daily. Treatment will continue until progression, intolerable toxicity or as per patient preference. Primary objective: To determine the efficacy of Olaparib monotherapy in stage IV pancreatic ductal adenocarcinoma (PDAC)with BRCAness (BRCA-Breast Cancer susceptibility gene).

Detailed Description

      An open label, single arm, phase II trial of Olaparib for PDAC patients with BRCAness
      (BRCA-Breast Cancer susceptibility gene).

      Patients with previously identified Loss of ATM (ATM serine/threonine kinase)by IHC OR-
      Family history of BRCA-associated cancers: breast, ovarian, pancreatic, gastric or prostate
      must be present in 2 or more first-degree relatives OR- Patients with previously identified
      genetic aberrations that are associated with HRD will be eligible [e.g. somatic BRCA
      mutation, Fanconi Anemia gene or RAD51(eukaryote gene) mutations].

      All patients will be retrospectively investigated for HRD(Homologous recombination repair
      deficiencies) signature using transcriptome profiling and ATM expression and the results
      correlated with PARPi (Polyadenosine 5'diphosphoribose [poly (ADP ribose)] polymerisation
      INHIBITOR) response rates.

      Eligible patients will receive treatment with Olaparib tablets p.o 300 mg twice daily until
      progression. Each treatment cycle is described as 28 days long. Patients will have tumor
      assessments according to RECIST 1.1(Response Evaluation Criteria In Solid Tumors) at
      baseline. Patients will then be followed for the final analysis of OS.

      Eligible patients will be those patients with stage IV pancreas cancer previously treated for
      metastatic disease. Patients must have received one prior therapy for the treatment of
      metastatic disease or refused chemotherapy.

      Following study entry, patients will attend clinic visits every two weeks for the first 4
      weeks of treatment (Days 1 and 15,). 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.

      Following discontinuation of study treatment, patients should be seen at 30 days post
      discontinuation for the evaluations outlined in the study schedule. Patients will be
      contacted in the 7 days following a specified date (data cut-off date) to capture survival
      status at that point for each survival analysis.

      Patients will have tumor assessments according to RECIST at baseline and every 8 weeks
      (±1week) up to 40 weeks and then every 12 weeks (±1 week) relative to date of enrolment until
      objective radiological disease progression according to modified RECIST criteria. Ongoing
      collection of site review tumor assessment is required and must be recorded in the electronic
      case report form (eCRF).

      Any patient who discontinues study treatment for reasons other than objective radiological
      progression should continue to undergo scheduled objective tumor assessments according to the
      study schedule,in order to assess objective radiological progression of disease. Failure to
      do so may result in bias to the study results.
    

Trial Arms

NameTypeDescriptionInterventions
Single ArmExperimentalOnly one Arm,All patients will receive Olaparib 300 mg (MILIGRAM)bid p.o till disease progression
  • OLAPARIB

Eligibility Criteria

        Inclusion Criteria:

          -  • Patients must be male or female ≥18 years of age

               -  Patients with histologically or cytologically confirmed metastatic adenocarcinoma
                  of the pancreas.

               -  Patients must have tested negative for BRCA 1 or 2 germline deleterious mutation
                  or be ineligible for BRCA testing [as determined by their insurer]

               -  Patients with previously identified Loss of ATM by IHC OR

               -  Family history of BRCA-associated cancers: breast, ovarian, pancreatic, gastric
                  or prostate must be present in 2 or more first-degree relatives OR

               -  Patients with previously identified genetic aberrations that are associated with
                  HRD will be eligible [e.g. somatic BRCA mutation, Fanconi Anemia gene or RAD51
                  mutations].

               -  Patients must have received at least one prior therapy for metastatic disease or
                  have refused chemotherapy to be eligible

               -  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. RECIST 1.1 has been modified to allow the assessment of
                  progression due to new lesions in patients with no evidence of disease at
                  baseline

               -  ECOG (Eastern Cooperative Oncology Group: A performance status using scales and
                  criteria to assess how a patient's disease is progressing)Performance Status 0-1
                  (Karnofsky >70).

               -  Patients must have adequate organ and marrow function as defined below:

          -  Leukocytes >3,000 cells/mm3

          -  Absolute neutrophil count >1,500 cells/mm3

          -  Platelets >100,000 cells/mm3

          -  Hemoglobin >9 g/dl (no blood transfusions within 4 weeks prior to enrolment)

          -  Total bilirubin <1.5 X institutional upper limit of normal (IULN)

          -  AST aspartate aminotransferase (SGOT)/ALT Alanine transaminase(SGPT) <2.5 X IULN
             without liver metastasis <5 X IULN for patients with liver metastasis

          -  Creatinine within normal institutional limits OR

          -  Creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above
             institutional normal

               -  INR(international normalized ratio ) <1.5

               -  Women of childbearing potential (defined as not post-menopausal for 12 months or
                  no previous surgical sterilization) and fertile men must agree to use adequate
                  contraception for the duration of study participation. Male subjects must agree
                  to refrain from sperm donation during the study and for 30 days after the last
                  dose of study drugs.

               -  Ability to understand and the willingness to sign a written informed consent
                  document. Signed informed consent form must be obtained prior to initiation of
                  study evaluations and/or activities.

        Exclusion Criteria:

          -  Uncontrolled intercurrent illness including symptomatic congestive heart failure,
             unstable angina pectoris, cardiac arrhythmia and myocardial infarction (MI) within 3
             months of initiation of therapy.

               -  Pregnancy or lactation

               -  Patient has active and uncontrolled bacterial, viral, or fungal infection(s)
                  requiring systemic therapy

               -  Patient has undergone major surgical resection within 4 weeks prior to
                  enrollment.

               -  Patient received radiotherapy, surgery, chemotherapy, or an investigational
                  therapy within 2 weeks prior to study entry.

               -  Patient has serious medical risk factors involving any of the major organ systems
                  such that the investigator considers it unsafe for the patient to receive an
                  experimental research drug

               -  Serious psychiatric or medical conditions that could interfere with treatment

               -  History of prior malignancy unless the malignancy has been treated with no
                  evidence of active disease and more than 2 years from initial diagnosis

               -  Major bleeding in the last 4 weeks prior to study entry
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR) by using RECIST 1.1
Time Frame:approximately- 24 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:approximately- 24 months
Safety Issue:
Description:
Measure:Progression Free Survival (PFS)
Time Frame:approximately- 24 months
Safety Issue:
Description:
Measure:Carbohydrate antigen (CA )19-9 response rate
Time Frame:approximately- 24 months
Safety Issue:
Description:
Measure:Number of adverse events (AEs) and serious adverse events (SAEs);
Time Frame:approximately- 24 months
Safety Issue:
Description:
Measure:Composite measure of dose interruptions, reductions and dose intensity
Time Frame:approximately- 24 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sheba Medical Center

Last Updated