Phase II Pilot Study of FOLFOXIRI Plus Panitumumab in Metastatic RAS Wild-type, Left-sided Colorectal Cancer

• Subjects must have signed an approved informed consent.

• Histologically confirmed diagnosis of advanced adenocarcinoma of the colon or rectum.

• No previous systemic chemotherapy for metastatic disease

‣ Subjects who have had prior adjuvant chemotherapy for non-metastatic disease are eligible if more than six months have elapsed after completing therapy

⁃ Subjects treated with adjuvant chemotherapy who relapse within six months after completion will not be eligible.

• Bidimensionally measurable disease as defined in Section 3.3.1.

• RAS wild-type tested in

‣ KRAS exon 2 (codons 12/13)

⁃ NRAS exon 2 (codons 12/13)

• ECOG Performance Status 0-1 (Appendix 1).

• Recovery in full, from any previous surgical procedure.

• Subjects \>=18 years of age. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 6 months after the study in such a manner that the risk of pregnancy is minimized.

• WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal.

• WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study medication.

• Creatinine clearance ≥ 50 ml/min or serum creatinine ≤ 1.5 x upper limit of normal.

⁃ Bilirubin ≤ 1.5 x upper limit of normal

⁃ AST, ALT ≤ 2.5 x upper limit of normal in absence of liver metastases, or ≤ 5 x upper limit of normal in presence of liver metastases,

⁃ Albumin within normal institutional limits

⁃ Magnesium ≥ lower limit of normal; calcium ≥ lower limit of normal .

⁃ Absolute Neutrophil Count \> 1500/mm3 and platelets \> 100,000/mm3.