Safety and Efficacy Study of mFOLFOX6 + Panitumumab Combination Therapy and 5-FU/LV + Panitumumab Combination Therapy in Participants With Chemotherapy-naïve Unresectable Advanced Recurrent Colorectal Carcinoma
Condition: Colorectal Carcinoma
MeSH terms: Carcinoma; Colorectal Neoplasms
Intervention: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab; oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab
Intervention description: oxaliplatin (OXA), levofolinate calcium (l-LV), panitumumab: intra-venous infusion 5-FU: bolus and continuous intra-venous infusion
Intervention MeSH terms: Calcium, Dietary; Leucovorin; Oxaliplatin; Fluorouracil; Panitumumab; Calcium; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 164.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Metastatic colorectal cancer, Panitumumab, mFOLFOX6, First-line

Summary:

      The purpose of this study is to exploratorily examine efficacy and safety in the participants
      with chemotherapy-naïve unresectable, advanced/recurrent colorectal carcinoma of Kirsten rat
      sarcoma-2 virus (KRAS) wild-type who have been treated with 6 cycles (2 weeks/cycle) of
      first-line mFOLFOX6 + panitumumab combination therapy and then assigned to two groups i.e., a
      group receiving 5-FU/LV + panitumumab combination therapy and a group receiving mFOLFOX6 +
      panitumumab combination therapy.
    

Eligibility criteria:

        Inclusion Criteria for enrollment:

          1. Participants with unresectable adenocarcinoma originating in the large intestine
             (excluding carcinoma of the appendix and anal canal cancer)

          2. Participants with measurable lesion(s) according to the RECIST ver. 1.1

          3. Participants who have not received chemotherapy for colorectal cancer. Participants
             who experience relapse more than 6 months after the final dose of perioperative
             adjuvant chemotherapy with fluoropyrimidine agents may be enrolled.

          4. Aged ≥ 20 years at the time of enrollment

          5. Participants classified as KRAS wild-type. However, the criteria will be changed to
             all patients who are verified to be of KRAS and NRAS wild-type when the KRAS and NRAS
             tests come to be covered by National Health Insurance, and the tests become feasible
             at medical institutions.

          6. Participants who satisfy the following criteria for the major organ function in tests
             performed within 14 days prior to enrollment

               1. Neutrophil count ≥ 1.5 × 10^3/μL

               2. White blood cell count ≥ 3.0 × 10^3/μL

               3. Platelet count ≥ 10.0 × 10^4/μL

               4. Hemoglobin ≥ 9.0 g/dL

               5. Total bilirubin ≤ 2.0 mg/dL

               6. AST ≤ 100 U/L (≤ 200 U/L if liver metastases are present)

               7. ALT ≤ 100 U/L (≤ 200 U/L if liver metastases are present)

               8. Serum creatinine ≤ 1.5 mg/dL

          7. Participants who are assessed at Eastern Cooperative Oncology Group (ECOG) performance
             status (P.S.) of 0 or 1

          8. Life expectancy of ≥ 6 months after enrollment

          9. Participants who have given written consent to take part in the study after detailed
             explanation of the study prior to enrollment

        Inclusion criteria for randomization:

          1. Participants who have received 6 cycles of mFOLFOX6 + panitumumab combination therapy

          2. Participants who are assessed at ECOG P.S. of 0-1 in the 6th cycle.

          3. Participants for whom PD or not evaluable has been denied on the RECIST 1.1 based on
             imaging tests conducted after the day of administration in the 6th cycle within 14
             days (2 weeks).

        Exclusion Criteria for enrollment:

          1. Radiotherapy received for a measurable lesion

          2. Radiotherapy received within 28 days (4 weeks) prior to enrollment for a lesion other
             than measurable lesions. However, treatment to relieve pain associated with metastatic
             bone tumors was allowed.

          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. Active hemorrhage requiring blood transfusion

          8. Disease requiring systemic steroids for treatment (excluding topical steroids)

          9. Intestinal resection and colostomy within 2 weeks prior to enrollment

         10. History or obvious and extensive CT findings of interstitial pulmonary disease
             (interstitial pneumonia, pulmonary fibrosis, etc.)

         11. Serious drug hypersensitivity

         12. Local or systemic active infection requiring treatment, or fever indicating infection

         13. Intestinal paralysis, gastrointestinal obstruction, or uncontrollable diarrhea
             (incapacitating symptoms despite adequate treatment)

         14. Active hepatitis B and/or active hepatitis C

         15. Known human immunodeficiency virus infection

         16. Other patients judged by the investigator or subinvestigator to be ineligible for
             enrollment in the study

        Exclusion criteria for randomization:

          1. Participants in whom interstitial pneumonia has been newly diagnosed during the period
             from registration to randomization

          2. Participants who have received radiotherapy during the period from registration to
             randomization

          3. Other Participants judged by the investigator or sub-investigator to be ineligible for
             enrollment in the study