Efficacy and Safety of PARPi to Treat Pancreatic Cancer

• Status: Unknown status
• Trial end date: 2017-10-01
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sheba Medical Center
• Treatments: Olaparib

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