Maintenance Rucaparib in BRCA1, BRCA2 or PALB2 Mutated Pancreatic Cancer That Has Not Progressed on Platinum-based Therapy
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: RUCAPARIB
Intervention description: Rucaparib is a PARP inhibitor used as an anti-cancer agent. Rucaparib is a first-in-class pharmaceutical drug targeting the DNA repair enzyme poly-ADP ribose polymerase-1.
Intervention MeSH terms: Rucaparib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The main purpose of this study is to look at the effectiveness, safety, and antitumor
      activity (preventing growth of the tumor) of the experimental study drug rucaparib (also
      known as CO-338) on subjects and on their pancreatic cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma with
             locally advanced or metastatic disease

          -  ≥18 years of age.

          -  Eastern Cooperative Oncology (ECOG) performance status of 0 to 1.

          -  Patients may have previously failed non-platinum containing therapy or may never have
             previously progressed on treatment.

          -  Patients must be on treatment with platinum-based (cisplatin, oxaliplatin or
             carboplatin) treatment for locally advanced or metastatic pancreatic cancer and have
             received a minimum of 16 weeks of therapy without evidence of disease progression
             based on the investigator's opinion.

          -  Discontinuation of the platinum component of the regimen for chemotherapy-related
             toxicity is permissible provided the patient has previously received at least 16 weeks
             of platinum-based therapy without evidence of disease progression ≤8 weeks after
             treatment with the platinum agent

          -  Documented deleterious BRCA1/2 or PALB2 mutation (germline or somatic) as assessed by
             CLIA certified laboratory. Variants that are considered to be non-detrimental
             ("Variants of uncertain significance", "Variants of unknown significance", "Variant,
             favor polymorphism" or "benign polymorphism" etc) are not sufficient for study entry.

          -  Measurable disease is not required for enrollment.

          -  Adequate organ function confirmed by the following laboratory values obtained ≤7 days
             prior to the first day of rucaparib:

               1. Absolute neutrophil count (ANC) ≥1.5 x 109/L

               2. Platelets>100 x 109/L

               3. Hemoglobin≥9g/dL

               4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x upper
                  limit of normal (ULN)

               5. Total bilirubin ≤1.5 x ULN; if liver metastases or metabolic disorder such as
                  Gilbert's syndrome, then ≤2.5 x ULN.

               6. Serum creatinine ≤1.5 x ULN or estimated glomerular filtration rate (GFR) ≥45
                  mL/min using Cockcroft Gault formula.

        Exclusion Criteria

          -  Prior treatment with a PARP inhibitor

          -  Patients who have demonstrated resistance to platinum agents (e.g. oxaliplatin,
             cisplatin) are not eligible to participate in this study

          -  Clinical evidence of uncontrolled malabsorption and/or any other gastrointestinal
             disorder or defect that would, in the opinion of the investigator, interfere with the
             absorption of rucaparib

          -  Acute infection requiring intravenous antibiotics, antiviral or antifungal agents
             during the 14 days prior to first dose of rucaparib

          -  Symptomatic or untreated CNS metastases.

          -  Expected life expectancy of <12 weeks as determined by the investigator.

          -  For fertile patient (female able to become pregnant or male able to father a child),
             refusal to use effective contraception during the period of the trial and for 6 months
             after the last dose of rucaparib.

          -  Received any systemic treatment for pancreatic cancer ≤14 days prior to first dose of
             rucaparib.

          -  Non-study related minor surgical procedure ≤5 days, or major surgical procedure ≤21
             days, prior to the first dose of rucaparib; in all cases, patients must be
             sufficiently recovered and stable before treatment administration.

          -  Active drug or alcohol use or dependence that would interfere with study compliance.

          -  Presence of any other condition that may increase the risk associated with study
             participation or may interfere with the interpretation of study results, and, in the
             opinion of the investigator, would make the patient inappropriate for entry into the
             study.