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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: mFOLFOX6 + panitumumab combination therapy; Drug: mFOLFOX6 + bevacizumab combination therapy

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 787

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan
    • Takeda Selected Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

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Exploratory Study (NCT02394834) who have consented to the secondary use of samples and genomic data and have not withdrawn their consent.

Description

Inclusion Criteria:

1. 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Exploratory Study (NCT02394834) who have consented to the secondary use of samples and genomic data and have not withdrawn their consent.
2. 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group P; mFOLFOX6 + panitumumab combination therapy; 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; 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
Group B; mFOLFOX6 + bevacizumab combination therapy; 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; 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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2021
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: August 26, 2021
• First Posted (Actual): September 1, 2021

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Panitumumab
• Other Study ID Numbers: Panitumumab-4006; jRCT1031210293 (Registry Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No