A Study Of PF-05212384 Plus FOLFIRI Versus Bevacizumab Plus FOLFIRI In Metastatic Colorectal Cancer

This is a multicenter, open label Phase 1b/2 study in patients with metastatic colorectal carcinoma. The Phase 1b will identify the dose of the combination of PF-05212384 plus FOLFIRI. The randomized, two-arm Phase 2 portion will compare the efficacy and safety of PF-05212384 plus FOLFIRI to that of bevacizumab plus FOLFIRI.

The study population will consist of patients with mCRC previously treated with an oxaliplatin-based regimen in the first line setting or who have progressed within 6 months of the end of an adjuvant oxaliplatin-based regimen.

• Drug: PF-05212384
  
  PF-05212384 at the Recommended phase 2 dose (RP2D/MTD) weekly
• Drug: FOLFIRI regimen
  
  The RP2D/MTD dose of FOLFIRI regimen every 2 weeks
• Biological: Bevacizumab
  
  5 mg/m^2 every 2 weeks or 7.5 mg/m^2 every 3 weeks
• Drug: FOLFIRI
  
  Full dose FOLFIRI regimen every 2 weeks

• Experimental: Arm A
  
  PF-05212384 plus FOLFIRI
  Interventions:
  

  • Drug: PF-05212384
  • Drug: FOLFIRI regimen
• Active Comparator: Arm B
  
  Bevacizumab plus FOLFIRI
  Interventions:
  

  • Biological: Bevacizumab
  • Drug: FOLFIRI

Inclusion Criteria:

• Advanced colorectal carcinoma.
• Progression on prior oxaliplatin-containing regimen used in 1st line setting for mCRC or progression within 6 months of end of oxaliplatin-containing regimen in the adjuvant setting.
• Tumor tissue available at time of screening for molecular profiling.
• Adequate performance status.
• Adequate glucose control, bone marrow, kidney, liver, and heart function.

Exclusion Criteria:

• Participation in other studies involving investigational drug(s) (Phases 1-4) before the current study begins and/or during study participation.
• Prior irinotecan treatment.
• Prior radiation to the pelvis or abdomen in the metastatic or locally advanced setting.
• History of Gilbert's syndrome.
• Active brain metastases.
• Deep vein thrombosis in the preceding 2 months.
• History of interstitial lung disease.
• RAS (KRAS/NRAS) wild type mCRC not previously treated with an anti-EGFR containing regimen (unless contraindicated or not considered standard practice per clinical site or country guidelines).