Study Of PF-03084014 In Combination With Gemcitabine And Nab-Paclitaxel In Patients With Metastatic Pancreatic Adenocarcinoma Not Previously Treated With Anticancer Therapies

• Drug: PF-03084014
  
  Tablets, orally administered twice daily on a continuous dosing schedule in 28 days cycles. Doses: 100 -150 mg BID
• Drug: Gemcitabine
  
  Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 1000 mg/m2.
• Drug: Nab-paclitaxel
  
  Intravenously administered on Days 1, 8, 15 in 28 days cycles at the dose of 125 mg/m2.
  Other Name: Abraxane
• Drug: PF-03084014
  
  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.

• Experimental: Phase 1
  
  PF-03084014 in combination with gemcitabine and nab-paclitaxel
  Interventions:
  

  • Drug: PF-03084014
  • Drug: Gemcitabine
  • Drug: Nab-paclitaxel
• Experimental: Phase 2 Arm A
  
  PF-03084014 in combination with gemcitabine and nab-paclitaxel
  Interventions:
  

  • Drug: PF-03084014
  • Drug: Gemcitabine
  • Drug: Nab-paclitaxel
• Active Comparator: Phase 2 Arm B
  
  Gemcitabine plus nab-Paclitaxel
  Interventions:
  

  • Drug: Gemcitabine
  • Drug: Nab-paclitaxel

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