Study of Single Agent Idelalisib Followed by Idelalisib in Combination With Chemotherapy in Adults With Metastatic Pancreatic Ductal Adenocarcinoma
Condition: Previously Untreated Pancreatic Ductal Adenocarcinoma; Relapsed/Refractory Pancreatic Ductal Adenocarcinoma
MeSH terms: Adenocarcinoma
Intervention: Idelalisib; Nab-paclitaxel; mFOLFOX6
Intervention description: Tablets administered orally twice daily; 125 mg/m^2 administered intravenously on Days 1, 8 and 15 of each 28 day cycle; mFOLFOX6 will be administered intravenously on Days 1 and 15 of each 28 day cycle. This regimen consists of levoleucovorin 200 milligram/meter per square (mg/m^2) or racemic leucovorin 400 mg/m^2, oxaliplatin 85 mg/m^2, bolus 5-fluorouracil 400 mg/m^2, and a 46 hour infusion of 5-fluorouracil 2, 400 mg/m^2.
Intervention MeSH terms: Paclitaxel; Idelalisib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to evaluate the safety of single agent idelalisib and
      to evaluate safety and define the maximum tolerated dose (MTD) of idelalisib in combination
      with chemotherapy in adults with metastatic pancreatic ductal adenocarcinoma.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  The presence of metastatic pancreatic adenocarcinoma plus 1 of the following:

               -  Histological diagnosis of pancreatic adenocarcinoma confirmed pathologically, OR

               -  Pathologist confirmed histological/cytological diagnosis of adenocarcinoma
                  consistent with pancreas origin

          -  Measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1

          -  Prior systemic chemotherapy treatment for metastatic pancreatic ductal adenocarcinoma
             (Arm: idelalisib single agent only)

          -  Received one prior line of chemotherapy for metastatic pancreatic ductal
             adenocarcinoma (Arm: idelalisib + mFOLFOX6 only)

          -  Adequate organ function defined as follows:

               -  Hepatic: Total bilirubin ≤ 1.25 x upper limit of normal (ULN) (Arm: idelalisib +
                  nab-paclitaxel ); total bilirubin ≤1.5 x ULN (Arm: single agent idelalisib and
                  Arm: idelalisib + mFOLFOX6); aspartate transaminase (AST) serum glutamic
                  oxaloacetic transaminase (SGOT), alanine transaminase (ALT) serum glutamic
                  pyruvic transaminase (SGPT) < 2.5 x ULN, and albumin > 3.0 g/dL

               -  Hematological: absolute neutrophil count (ANC) > 1,500 cells/cubic millimetre
                  (m^3), platelet > 100,000 cells/mm^3, hemoglobin > 9.0 grams/decilitre (g/dL)

               -  Renal: Serum creatinine ≤ 1.5 x ULN OR calculated creatinine clearance (CrCl) >
                  30 millilitre (ml)/min as calculated by the Cockcroft-Gault method

          -  Able to comprehend and willing to sign the written informed consent form

        Key Exclusion Criteria:

          -  Currently or previously treated with biologic, or immunotherapy

          -  Currently or previously treated with conventional chemotherapy, or other agents for
             metastatic pancreatic ductal adenocarcinoma (Arm: idelalisib + nab-paclitaxel only)

          -  Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of
             enrollment

          -  Known human immunodeficiency viruses (HIV) infection

          -  History of a concurrent or second malignancy except for adequately treated local basal
             cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial
             bladder cancer, asymptomatic prostate cancer without known metastatic disease and with
             no requirement for therapy or requiring only hormonal therapy and with normal
             prostate-specific antigen for ≥ 1 year prior to enrollment, adequately treated Stage 1
             or 2 non-pancreatic cancer currently in complete remission, or any other
             non-pancreatic cancer that has been in complete remission for ≥ 5 years

          -  Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non-adenocarcinoma (eg,
             lymphoma, sarcoma), adenocarcinoma originating from the biliary tree or
             cystadenocarcinoma

          -  History of serious allergic reaction, including anaphylaxis and toxic epidermal
             necrolysis

          -  Presence of peripheral neuropathy ≥ Grade 2 (Arm: idelalisib + nab-paclitaxel and Arm:
             idelalisib + mFOLFOX6)

          -  Documented myocardial infarction or unstable/uncontrolled cardiac disease (eg,
             unstable angina, congestive heart failure [New York Heart Association > Class III])
             within 6 months or enrollment

          -  Known hypersensitivity to idelalisib, its metabolites, or formulation excipients

          -  Known hypersensitivity to nab-paclitaxel (Arm: idelalisib + nab-paclitaxel), their
             metabolites, or formulation excipients

          -  Known hypersensitivity to 5-fluorouracil, leucovorin, or oxaliplatin (Arm: idelalisib
             + mFOLFOX6), their metabolites, or formulation excipients

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.