An Additional Analysis of Data From the PARADIGM Exploratory Study (NCT02394834) in Patients With Advanced/Recurrent Colorectal Cancer

Study Overview
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Brief Summary
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The main aim of the study is to check gene change in tumor tissues with an additional analysis of the data from PARADIGM Exploratory Study, which is conducted for people with advanced/recurrent colorectal cancer. In the PARADIGM Exploratory Study (NCT02394834), the drug being tested in this study is called Panitumumab and the main aim of this study is to check side effect from the study treatment (mFOLFOX6 + bevacizumab versus mFOLFOX6 + panitumumab therapy) and check if the study treatment improves symptoms of advanced/recurrent colorectal cancer.

Detailed Description
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This is a non-interventional study to do additional exploratory analysis of biomarkers from the PARADIGM Exploratory Study (NCT02394834), which is conducted for participants with advanced/recurrent colorectal cancer. 757 patients have enrolled in the PARADIGM Exploratory Study.

Official Title
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Additional Exploratory Analysis of Biomarkers in the PARADIGM Exploratory Study in Patients With Advanced/Recurrent Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: mFOLFOX6 + panitumumab combination therapy
* Drug: mFOLFOX6 + bevacizumab combination therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants enrolled in the PARADIGM Exploratory Study (NCT02394834) who have consented to the secondary use of samples and genomic data and have not withdrawn their consent. Participants with sufficient surplus samples for gene expression/mutation and pathomorphologic (IHC, IF and/or ISH, etc.) analysis. Exclusion Criteria: Participants who are considered inappropriate for participation in this study by the research institution.

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: mFOLFOX6 + panitumumab combination therapy<br>* oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab 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: mFOLFOX6 + bevacizumab combination therapy<br>* oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, bevacizumab 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 gene expression levels in tumor tissues at the baseline of the main study to evaluate the relationship between OS and gene expression. 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 | 
| Progression-Free Survival (PFS) | PFS obtained in the main study will be stratified by the gene expression levels in tumor tissues at the baseline of the main study to evaluate the relationship between the PFS and gene expression. 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Correlation between Each Gene Mutations in Plasma Free DNA at Baseline of Main Study, and Efficacy Endpoints (OS and PFS) |  | Up to approximately 63 months | 
| Evaluation of Correlation between Each Gene Expression Levels in Tumor Tissue at Baseline of Main Study, and Efficacy Endpoints (OS and PFS) |  | Up to approximately 63 months | 
| Evaluation of Correlation between Change in Each Gene Mutations in Plasma Free DNA at Baseline and Discontinuation of Protocol Treatment of Main Study, and Efficacy Endpoints (OS and PFS) |  | Up to approximately 63 months | 
| Evaluation of Correlation between Change in Each Gene Expression Levels in Tumor Tissue at Baseline and Discontinuation of Protocol Treatment of Main Study, and Efficacy Endpoints (OS and PFS) |  | Up to approximately 63 months | 
| Evaluation of Correlation between High Gene Expression Region in Tumor Tissue at Baseline of Main Study, and Efficacy Endpoints (OS and PFS) |  | Up to approximately 63 months | 
| Evaluation of Correlation between Change in Gene Expression Region in Tumor Tissue at Baseline and Discontinuation of Protocol Treatment of Main Study, and Efficacy Endpoints (OS and PFS) |  | Up to approximately 63 months |