A Study Of PF-05212384 Plus Irinotecan Vs Cetuximab Plus Irinotecan In Patients With KRAS And NRAS Wild Type Metastatic Colorectal Cancer

• Drug: PF-05212384
  30 minute IV infusion of PF-05212384 on days 2, 9, 16 and 23 of each cycle. Intra-patient dose escalation will commence with 110mg and will increase depending on tolerability.
  Other Name: PKI-587
• Drug: irinotecan
  90 minutes IV infusion of irinotecan 180mg/m^2 on days 1 and 15 of each cycle
  Other Name: Camptosar, Campto, CPT-11
• Drug: Cetuximab
  120 minute IV infusion of cetuximab 400mg/m^2 on cycle 1 day 1; 60 minute IV infusion of cetuximab on days 8, 15, and 22 of each cycle, and on day 1 of each cycle after cycle 1
  Other Name: Erbitux
• Drug: Irinotecan
  90 minutes IV infusion of Irinotecan 180mg/m^2 on days 1 and 15 of each cycle
  Other Name: Camptosar, Campto, CPT-11

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

  • Drug: PF-05212384
  • Drug: irinotecan
• Active Comparator: Arm B
  Cetuximab plus Irinotecan
  Interventions:

  • Drug: Cetuximab
  • Drug: Irinotecan

Inclusion Criteria:

• KRAS and NRAS wild type metastatic colorectal cancer
• Progression following treatment for colorectal cancer with irinotecan, oxaliplatin and fluoropyrimidine therapy in the metastatic setting.
• Eastern Cooperative Oncology Group [ECOG] Performance Status of 0, 1, or 2
• At least one measurable lesion by Response Evaluation Criterion in Solid Tumors [RECIST]

Exclusion Criteria:

• More than 2 prior cytotoxic chemotherapy regimens for metastatic colorectal cancer.
• Prior treatment with a PI3K, mTOR, AKT or EGFR inhibitor
• Patients who have discontinued treatment with prior irinotecan therapy due to toxicity.
• Prior radiation to the pelvis or abdomen
• Patients with history of interstitial lung disease.