An Exploratory Study of Treatment Sensitivity and Prognostic Factors in a Efficacy and Safety Study of mFOLFOX6 + Bevacizumab Versus mFOLFOX6 + Panitumumab Therapy in Patients With Chemotherapy-naïve Unresectable Advanced or Recurrent Colorectal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to investigate biomarkers which may be predictors of efficacy and safety of treatment with mFOLFOX6 + bevacizumab versus mFOLFOX6 + panitumumab therapy in patients with chemotherapy-naïve unresectable advanced or recurrent colorectal cancer.

Detailed Description
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The drug being tested in this study is called Panitumumab. This exploratory study will investigate biomarkers which may be predictors of efficacy and safety of treatment with mFOLFOX6 + bevacizumab versus mFOLFOX6 + panitumumab therapy in patients with chemotherapy-naïve unresectable advanced or recurrent colorectal cancer. Tumor tissue samples obtained from the participants who enrolled in the safety/efficacy study of Panitumumab + mFOLFOX versus bevacizumab + mFOLFOX (PARADIGM Study: NCT02394795) and provided consent for this additional study will be used. Mutations, amplification and rearrangement of predefined tumor-associated genes will be investigated using DNA collected from tumor samples used for assessing RAS mutations and plasma free DNA collected before administration of cycle 1 and at the discontinuation of the protocol treatment in the main study.

Official Title
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An Exploratory Study of Treatment Sensitivity and Prognostic Factors in a Phase III, Randomized, Controlled Study Comparing the Efficacy and Safety of mFOLFOX6 + Bevacizumab Therapy vs. mFOLFOX6 + Panitumumab Therapy in Patients With Chemotherapy-naïve Wild-type RAS(KRAS/NRAS) Unresectable Advanced or Recurrent Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab
* Drug: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1) Patients who are enrolled in the main study and personally provided written consent after adequately explained about the contents of the additional study Exclusion Criteria: (1) Patients who are determined by the investigator or researchers to be not suitable for participating in the additional study

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group P; mFOLFOX6 + panitumumab combination therapy<br>OXA: 85 mg/m2/day 1 l-LV: 200 mg/m2/day 1 5-FU iv: 400 mg/m2/day 1 5-FU civ: 2400 mg/m2/day 1-3 panitumumab: 6 mg/kg mFOLFOX6 + panitumumab combination therapy, once every two weeks | Drug: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab<br>* oxaliplatin (OXA), levofolinate calcium (l-LV), panitumumab: intra-venous infusion 5-FU: bolus and continuous intra-venous infusion<br>|
| Group B; mFOLFOX6 + bevacizumab combination therapy<br>OXA: 85 mg/m2/day 1 l-LV: 200 mg/m2/day 1 5-FU iv: 400 mg/m2/day 1 5-FU civ: 2400 mg/m2/day 1-3 bevacizumab: 5 mg/kg/ mFOLFOX6 + bevacizumab combination therapy, once every two weeks | Drug: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, bevacizumab<br>* oxaliplatin (OXA), levofolinate calcium (l-LV), bevacizumab: intra-venous infusion 5-FU: bolus and continuous intra-venous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | OS obtained in the main study will be stratified by the presence or absence of mutation of tumor-associated genes in tumor tissues at the baseline of the main study to evaluate the relationship between OS and gene mutations. OS will be measured as the time from the date of randomization to the date of death due to any causes. | Up to approximately 63 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS obtained in the main study will be stratified by the presence or absence of mutation of tumor-associated genes in tumor tissues at the baseline of the main study to evaluate the relationship between the efficacy endpoint and gene mutations. PFS is defined as the time from the date of randomization to the earlier of Progressive Disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or death due to any cause. | Up to approximately 63 months | 
| Response Rate (RR) | RR obtained in the main study will be stratified by the presence or absence of mutation of tumor-associated genes in tumor tissues at the baseline of the main study to evaluate the relationship between the efficacy endpoint and gene mutations. RR is defined as percentage of participants who achieve Complete Response (CR) and Partial Response (PR) as the best overall response per RECIST version 1.1. | Approximately 12 months | 
| Duration of Response (DOR) | DOR obtained in the main study will be stratified by the presence or absence of mutation of tumor-associated genes in tumor tissues at the baseline of the main study to evaluate the relationship between the efficacy endpoint and gene mutations. DOR means that the period from the day when either CR or PR is first confirmed until the day of documented PD or the day of death due to all causes, whichever occurs earlier. | Up to approximately 63 months | 
| Percentage of Participants who Proceeded to Surgical Resection | The outcome obtained in the main study will be stratified by the presence or absence of mutation of tumor-associated genes in tumor tissues at the baseline of the main study to evaluate the relationship between the efficacy endpoint and gene mutations. | Up to approximately 63 month | 
| Percentage of Participants with Early Tumor Shrinkage | The outcome obtained in the main study will be stratified by the presence or absence of mutation of tumor-associated genes in tumor tissues at the baseline of the main study to evaluate the relationship between the efficacy endpoint and gene mutations. | Up to approximately 63 months | 
| Degree of the Maximum Tumor Shrinkage (Depth of Response) | The outcome obtained in the main study will be stratified by the presence or absence of mutation of tumor-associated genes in tumor tissues at the baseline of the main study to evaluate the relationship between the efficacy endpoint and gene mutations. | Up to approximately 63 months | 
| Evaluation of the Relationship of Each Biomarker in Plasma Free DNA and Tumor Samples at Baseline of the Main Study |  | Up to approximately 63 months | 
| Evaluation of the Relationship between Each Biomarker in Plasma Free DNA at Baseline of the Main Study, and Efficacy Endpoints |  | Up to approximately 63 months | 
| Evaluation of the Relationship between a Change in Each Biomarker in Plasma Free DNA at Baseline and the Discontinuation of the Protocol Treatment of the Main Study, and Efficacy Endpoints |  | Up to approximately 63 months | 
| Evaluation of the Relationship between a Change in Each Biomarker in Tumor Tissue at Baseline and the Discontinuation of the Protocol Treatment of the Main Study, and Efficacy Endpoints |  | Up to approximately 63 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic colorectal cancer, Panitumumab, mFOLFOX6, Bevacizumab