Panitumumab, Leucovorin Calcium, and Fluorouracil after Combination Chemotherapy and Panitumumab Induction in Treating Patients with RAS Wild Type Locally Advanced or Metastatic Colorectal Cancer That Cannot Be Removed by Surgery

Inclusion Criteria

• Metastatic or locally advanced (unresectable) colorectal cancer with histological confirmation of adenocarcinoma (patients with or without measurable disease by imaging are eligible)
• No prior systemic chemotherapy for metastatic disease; subjects who received adjuvant therapy with FOLFOX and at the time of recurrence are at least 6 months away from last chemotherapy are eligible for this study
• Provide written informed consent
• RAS wild‐type tumor
• Negative serum or urine pregnancy test done =< 7 days prior to registration, for women of childbearing potential only * Childbearing potential is defined as a female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not postmenopausal (defined as amenorrhea >= 12 consecutive months; or women on hormone replacement therapy with documented serum follicle stimulating hormone level > 35 mIU/mL); women who are using oral, implanted, or injectable contraceptive hormones or mechanical products such as intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or who are practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of childbearing potential
• Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0 or 1
• Total serum bilirubin =< institutional upper limit of normal (ULN) (=< 14 days prior to on study [start of FOLFOX + panitumumab])
• Absolute neutrophil count (ANC) >= 1500/mm^3 (=< 14 days prior to on study [start of FOLFOX + panitumumab])
• Platelet count >= 100,000/mm^3 (=< 14 days prior to on study [start of FOLFOX + panitumumab])
• Hemoglobin >= 9.0 g/dL (hemoglobin may be supported by transfusion) (=< 14 days prior to on study [start of FOLFOX + panitumumab])
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer) (=< 14 days prior to on study [start of FOLFOX + panitumumab])
• Creatinine within institutional limits of normal OR creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (=< 14 days prior to on study [start of FOLFOX + panitumumab])
• Magnesium >= lower limit of normal (=< 14 days prior to on study [start of FOLFOX + panitumumab])
• Willing to provide tissue and blood samples for mandatory correlative and research purposes

Exclusion Criteria

• Patients who are candidates for up front metastasectomy * Defined as those with limited liver metastatic disease; the candidacy for resectability can be determined by the treating physician and or local surgeon; in ambiguous situations, please discuss the case with the principle investigator (PI)
• Known or suspected brain or central nervous system (CNS) metastases
• Active, uncontrolled infection, including hepatitis B, hepatitis C
• Patients with history of interstitial lung disease/pulmonary fibrosis
• Concurrent anti‐cancer therapy, including chemotherapy agents, targeted agents, or biological agents not otherwise specified in this protocol
• Radiation therapy =< 2 weeks prior to initiation of FOLFOX + panitumumab
• Any of the following * Pregnant or nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception
• Co‐morbid systemic illnesses or other severe concurrent disease, history of any psychiatric or addictive disorder, or laboratory abnormality, which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Patients known to be human immunodeficiency virus (HIV) positive
• Uncontrolled intercurrent illness whom in the opinion of the investigator, may increase the risks associated with study participation or study treatment, or may interfere with the conduct of the study or the interpretation of the study results
• Receiving any other investigational agent, which would be considered as a treatment for the primary neoplasm
• Other active malignancy =< 3 years prior to registration; exceptions are: non-melanoma skin cancer or carcinoma‐in‐situ of the cervix that has been treated
• History of prior malignancy for which patient is receiving other specific treatment for their cancer
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs