Clinical Trials /

Olaparib in Treating Patients With Stage IV Pancreatic Cancer

NCT02677038

Description:

This phase II trial studies how well olaparib works in treating patients with stage IV pancreatic cancer. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Olaparib in Treating Patients With Stage IV Pancreatic Cancer
  • Official Title: Olaparib for BRCAness Phenotype in Pancreatic Cancer: Phase II Study

Clinical Trial IDs

  • ORG STUDY ID: 2015-0503
  • SECONDARY ID: NCI-2016-00351
  • SECONDARY ID: 2015-0503
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT02677038

Conditions

  • Metastatic Pancreatic Adenocarcinoma
  • Pancreatic Ductal Adenocarcinoma
  • Stage IV Pancreatic Cancer AJCC v6 and v7

Interventions

DrugSynonymsArms
OlaparibAZD 2281, AZD-2281, AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281Treatment (olaparib)

Purpose

This phase II trial studies how well olaparib works in treating patients with stage IV pancreatic cancer. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the efficacy of olaparib monotherapy in stage IV pancreatic ductal
      adenocarcinoma (PDAC) with breast cancer, early onset (BRCA)ness.

      SECONDARY OBJECTIVES:

      I. To further determine the efficacy of olaparib in the study population.

      SAFETY OBJECTIVES:

      I. To assess the safety and tolerability of olaparib.

      EXPLORATORY OBJECTIVES:

      I. To identify tissue based biomarkers of defective homologous recombination repair (HRD).

      OUTLINE:

      Patients receive olaparib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28
      days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and then every 8
      weeks thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (olaparib)ExperimentalPatients receive olaparib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Olaparib

Eligibility Criteria

        Inclusion Criteria:

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

          -  Family history: one or more close blood relative with ovarian carcinoma at any age or
             breast cancer age 50 or younger or two relatives with breast, pancreatic or prostate
             cancer (Gleason 7 or higher) at any age, or patients with Ashkenazi Jewish ancestry;
             however, patients with previously identified genetic aberrations that are associated
             with homologous recombination deficiency (HRD) will be eligible even in the absence of
             family history (e.g. somatic BRCA mutation, Fanconi anemia gene, ATM or RAD51
             mutations)

          -  Patients must be germline BRCA 1 or 2 negative; (Note: if BRCA status was previously
             determined, that result is acceptable but documentation of status must be available;
             subjects with unknown status will be referred to genetic counselling for BRCA testing
             as per standard of care) and/or patients with previously identified genetic
             aberrations that are associated with HRD will be eligible even in the absence of
             family history (e.g. somatic BRCA mutation, Fanconi Anemia gene, ATM or RAD51
             mutations)

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

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as >=
             20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT)
             scan

          -  All treated patients have the option to undergo pre-treatment biopsy (liver, omentum,
             lung or lymph node) to be eligible

          -  Patients with prior malignancy and treated with no evidence of active disease, and
             more than 2 years from initial diagnosis are eligible

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky > 70)

          -  Leukocytes >= 3,000 cells/mm^3

          -  Absolute neutrophil count >= 1,500 cells/mm^3

          -  Platelets >= 75,000 cells/mm^3

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

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

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x IULN without liver metastasis; =< 5 x IULN for patients with liver metastasis

          -  Creatinine not greater than upper institutional limits OR creatinine clearance >= 60
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

          -  International normalized ratio (INR) < 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 two highly
             effective forms of contraception while they are receiving study treatment and for 30
             days after last dose of study drug; 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

          -  Patients whose tumors are deemed to be platinum-refractory will be excluded from the
             trial

          -  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

          -  Major bleeding in the last 4 weeks prior to study entry

          -  Concomitant use of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
             inhibitors

          -  Resting electrocardiogram (ECG) with corrected QT interval (QTc) > 470 msec
             (Fridericia's scale)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (defined as complete response or partial response) assessed using Response Evaluation Criteria in Solid Tumors 1.1
Time Frame:At 24 weeks
Safety Issue:
Description:Simon's optimal two-stage design will be implemented for the study. The objective response rate and its corresponding exact 95% confidence interval will be estimated.

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:Time from date of study entry to the date of death from any cause or to the date of last follow-up if patients are alive, assessed up to 3 years
Safety Issue:
Description:The Kaplan-Meier method will be used to estimate the probability of OS. The Log rank test and Cox proportional hazards models will be used to determine the association of OS with patient characteristics.
Measure:Progression free survival (PFS)
Time Frame:Time from the date of study entry to the date of progression or to the date of death from any cause, whichever occurred first, or to the last follow-up date if patients are alive without disease progression, assessed up to 3 years
Safety Issue:
Description:The Kaplan-Meier method will be used to estimate the probability of PFS. The Log rank test and Cox proportional hazards models will be used to determine the association of PFS with patient characteristics.
Measure:Change in cancer antigen 19-9 (CA19-9) clinical response
Time Frame:Baseline to up to 8 weeks
Safety Issue:
Description:Defined as the percentage reduction before and after 8 weeks of treatment. The mean, standard deviation, median and range will be summarized for the percentage reduction of CA 19-9.
Measure:Incidence of unacceptable toxicity
Time Frame:Up to 30 days after the completion of study treatment
Safety Issue:
Description:Defined as treatment related grade 3 or higher toxicities graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Unacceptable toxicities will be monitored closely using the method of Thall et al.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

June 10, 2019