Study Of PF-03084014 In Combination With Gemcitabine And Nab-Paclitaxel In Patients With Metastatic Pancreatic Adenocarcinoma Not Previously Treated With Anticancer Therapies
Condition: Metastatic Cancer Pancreas
MeSH terms: Adenocarcinoma
Intervention: PF-03084014; Gemcitabine; Nab-paclitaxel; PF-03084014; Gemcitabine; Nab-paclitaxel; Gemcitabine; Nab-paclitaxel
Intervention description: Tablets, orally administered twice daily on a continuous dosing schedule in 28 days cycles. Doses: 100 -150 mg BID; Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 1000 mg/m2.; Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 125 mg/m2.; Tablets, orally administered twice daily on a continuous dosing schedule in 28 days cycles. Phase 2 dose will be the recommended phase 2 dose defined in phase 1.; Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 1000 mg/m2.; Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 125 mg/m2.; Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 1000 mg/m2.; Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 125 mg/m2.
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine; Nirogacestat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study consists of a Phase 1b portion aimed to determine the maximum tolerated dose and
      the safety profile of PF-03084014 in combination with gemcitabine and nab-paclitaxel followed
      by a Phase 2 portion to evaluate the efficacy of the triple combination in terms of overall
      survival in patients with metastatic pancreatic ductal adenocarcinoma not previously treated
      with anticancer therapies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically diagnosis of metastatic ductal adenocarcinoma of the
             pancreas.

          -  No prior radiotherapy, surgery chemotherapy or investigational therapy for metastatic
             disease. Prior adjuvant therapy with 5-FU or gemcitabine (± gemcitabine post
             radiation) administered as radiosensitizer allowed, provided at least 6 months have
             elapsed between the last dose and study registration

          -  Tumor tissue available (Archival 6 months old or de novo biopsy)

          -  Measurable disease as per RECIST 1.1

          -  Performance Status (ECOG) 0 or 1

        Exclusion Criteria:

          -  Symptomatic brain metastases requiring steroids

          -  Prior therapy with gamma secretase inhibitors or other Notch pathway inhibitor

          -  Major surgery within 4 weeks of registration in the current study

          -  Known hypersensitivity to gemcitabine or nab-paclitaxel or any of the excipients

          -  Current or anticipated need for food or drugs that are strong/moderate CYP3A4
             inhibitors or inducers

          -  Diagnosis of any second malignancy within 3 years prior to registration