Panitumumab and RAS, Diagnostically-useful Gene Mutation for mCRC
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab; oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, bevacizumab
Intervention description: oxaliplatin (OXA), levofolinate calcium (l-LV), panitumumab: intra-venous infusion 5-FU: bolus and continuous intra-venous infusion; oxaliplatin (OXA), levofolinate calcium (l-LV), bevacizumab: intra-venous infusion 5-FU: bolus and continuous intra-venous infusion
Intervention MeSH terms: Calcium, Dietary; Leucovorin; Bevacizumab; Panitumumab; Oxaliplatin; Fluorouracil; Calcium; Levoleucovorin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 823.0
Sex: All
Minimum age: 20 Years
Maximum age: 79 Years
Healthy volunteers: No
Keywords: Metastatic colorectal cancer, Panitumumab, mFOLFOX6, Bevacizumab

Summary:

      The purpose of this study is to verify the efficacy of mFOLFOX6 + panitumumab combination
      therapy and mFOLFOX6 + bevacizumab combination therapy in first-line treatment of
      chemotherapy-naive patients with KRAS/NRAS wild-type, incurable/unresectable,
      advanced/recurrent colorectal cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Investigator and subinvestigator judge a candidate is understand clinical trial and
             comply this protocol.

             Investigator is those who participate in conducting a study and oversight the study
             duties at a site.

          2. Patients who have given written consent to take part in the study after detailed
             explanation of the study prior to enrollment

          3. Aged ≥20 to <80 years at the time of informed consent

          4. Patients with unresectable adenocarcinoma originating in the large intestine
             (excluding carcinoma of the appendix and anal canal cancer)

          5. Patients with lesion(s) that can be evaluated. It is not essential to be evaluated the
             tumor according to the RECIST ver. 1.1.

          6. Patients who have not received chemotherapy for colorectal cancer. Patients who
             experience relapse more than 24 weeks (168 days) after the final dose of perioperative
             adjuvant chemotherapy with fluoropyrimidine agents may be enrolled. Patients who have
             received perioperative adjuvant chemotherapy including oxaliplatin are excluded.

          7. Patients 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.

             Patients with no mutation in any of the codons shown below are considered wild type.
             It is not considered wild type if either of the codons are not evaluable or not
             tested.

             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. Patients 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 ≥ 9.0 g/dL

               -  Total bilirubin ≤ 2.0 mg/dL

               -  AST ≤ 100 IU/L (≤ 200 IU/L if liver metastases are present)

               -  ALT ≤ 100 IU/L (≤ 200 IU/L if liver metastases are present)

               -  Serum creatinine ≤ 1.5 mg/dL

               -  PT-INR < 1.5 (< 3.0 for patients treated with oral warfarin)

               -  Satisfies at least one of these conditions

                    1. Urine protein (dip stick method) ≤ 1+

                    2. UPC (urine protein creatinine) ratio ≤ 1.0

                    3. Urinary protein ≤ 1000 mg/ 24hours

          9. ECOG performance status (PS) of 0 or 1

         10. Life expectancy of ≥ 3 months (90 days) after enrollment

        Exclusion Criteria:

          1. Radiotherapy received within 4 weeks (28 days) prior to enrollment. Treatments aimed
             at relieving pain for bone metastases are excluded.

          2. Known brain metastasis or strongly suspected of brain metastasis

          3. 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.).

          4. Body cavity fluid that requires treatment (pleural effusion, ascites, pericardial
             effusion, etc.)

          5. Patients who do not want to use contraception to prevent pregnancy, and women who are
             pregnant or breast-feeding, or test positive for pregnancy

          6. Nonhealing surgical wound (excluding implanted venous reservoirs)

          7. Active hemorrhage requiring blood transfusion

          8. Disease requiring systemic steroids for treatment (excluding topical steroids)

          9. The patient who has placed colonic stent

         10. Intestinal resection within 4 weeks prior to enrollment or colostomy within 2 weeks
             prior to enrollmentt

         11. History or obvious and extensive CT findings of interstitial pulmonary disease
             (interstitial pneumonia, pulmonary fibrosis, etc.)

         12. Patients with unstable angina, myocardial infarction, cerebral hemorrhage, arterial
             thromboembolism such as cerebral infarction, or have history of these desease less
             than 24 weeks (168 days) before registration (except for lacunar infarction
             asymptomatic)

         13. Serious drug hypersensitivity

         14. Local or systemic active infection requiring treatment, or fever indicating infection

         15. NYHA class II or higher heart failure or serious heart disease

         16. Intestinal paralysis, gastrointestinal obstruction, or uncontrollable diarrhoea
             (incapacitating symptoms despite adequate treatment)

         17. Poorly controlled hypertension

         18. Poorly controlled diabetes mellitus

         19. Active hepatitis B

         20. Known HIV infection

         21. Peripheral neuropathy of ≥ Grade 2 by CTCAE (Japanese edition JCOG version 4.03)

         22. Other patients judged by the investigator or subinvestigator to be ineligible for
             enrollment in the study (e.g. Patients who might agree to participate under
             compulsion).