A Phase I/II Study for the Safety and Efficacy of Panitumumab in Combination With TAS-102 for Patients With Colorectal Cancer

Inclusion Criteria: 1. Investigator and subinvestigator judge a candidate is understand clinical trial and comply this protocol. 2. Participants who have given written consent to take part in the study after detailed explanation of the study prior to enrollment 3. Aged ≥20 to \<75 years at the time of informed consent 4. Participants with unresectable adenocarcinoma originating in the large intestine (excluding carcinoma of the appendix and anal canal cancer) 5. Participants with lesion(s) that can be evaluated. It is essential to be evaluated the tumor according to the Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1. 6. Participants who have received chemotherapies for metastatic colorectal cancer and are refractory to or failing those chemotherapies\* including; fluoropyrimidines, irinotecan, oxaliplatin, and an angiogenesis inhibitors. \*: Refractory to or failing those chemotherapies are defied as following; * If recurrence is observed by imaging during neoadjuvant/adjuvant therapy, or within 6 months of the completion of adjuvant therapy. * If imaging or clinical progression is observed during or within 3 months of the last dose of chemotherapy for advanced cancer. * When it is determined that the drugs (ie, fluropyrimidines, oxaliplatin, irinotecan, and angiogenesis inhibitors) are not allowed to be resume due to intolerable AE toxicities (eg, serious allergic reaction and accumulative neuropathy). 7. Participants classified as KRAS/NRAS wild-type\*\* by KRAS/NRAS testing\*. \*: KRAS/NRAS test will be performed using the in vitro diagnostic listed in the National Health Insurance. \*\*: Participants with no mutation in any of the codons shown below are considered wild type. KRAS: EXON2 (codon 12, 13), EXON3 (codon 59, 61), EXON4 (codon 117, 146) NRAS：EXON2 (codon 12, 13), EXON3 (codon 59, 61),EXON4 (codon 117, 146) 8. Participants are able to take medications orally. 9. Participants who satisfy the following criteria for the major organ function in tests performed within 14 days prior to enrollment * Neutrophil count ≥1.5×10\^3/µL * Platelet count ≥1.0×10\^4/µL * Hemoglobin ≥8.0 g/dL * Total bilirubin ≤1.5 mg/dL * Aspartate aminotransferase (AST) ≤ 100 IU/L ( ≤200 IU/L if liver metastases are present) * Alanine aminotransferase (ALT) ≤ 100 IU/L ( ≤200 IU/L if liver metastases are present) * Serum creatinine ≤ 1.5 mg/dL 10. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 11. Life expectancy of ≥ 3 months (90 days) after enrollment Exclusion Criteria: 1. Has received anti-EGFR antibodies (cetuximab or panitumumab), regorafenib, or TAS-102. 2. Has had treatment with radiotherapy and/or chemotherapy within 2 weeks (14 days) prior to study drug administration (except for limited field radiation in order to rescue of pain). 3. Known brain metastasis or strongly suspected of brain metastasis 4. Synchronous cancers or metachronous cancers with a disease-free period of ≥ 5 years (excluding colorectal cancer) excluding mucosal cancers cured or be possibly cured by regional resection (esophageal, stomach, and cervical cancer, non-melanoma skin cancer, bladder cancer, etc.). 5. Body cavity fluid that requires treatment (pleural effusion, ascites, pericardial effusion, etc.) 6. Participants who do not want to use contraception to prevent pregnancy, and women who are pregnant or breast-feeding, or test positive for pregnancy 7. Any investigational agent received within prior 4 weeks (28 days). 8. Disease requiring systemic steroids for treatment (excluding topical steroids) 9. History or obvious and extensive CT findings of interstitial pulmonary disease (interstitial pneumonia, pulmonary fibrosis, etc.) 10. Intestinal paralysis, gastrointestinal obstruction, or uncontrollable diarrhea (incapacitating symptoms despite adequate treatment. 11. Serious drug hypersensitivity (without allergy to oxaliplatin) 12. Local or systemic active infection requiring treatment, or fever indicating infection 13. NYHA class II or higher heart failure or serious heart disease 14. Active hepatitis B 15. Known HIV infection 16. Adverse event due to previous treatment that has not recovered to Grade 1 (Grade 2 for peripheral sensory neuropathy) by CTCAE (Japanese edition JCOG version 4.03) (excluding hemoglobin content) 17. Known BRAF mutation 18. Other participants judged by the investigator or subinvestigator to be ineligible for enrollment in the study (such as patients who were coerced to give consent)