Immunoscore as Decision Guidance for Adjuvant Chemotherapy in Colon Cancer (iMAGINE)

iMmunoscore Associated Decision GuIdance for adjuvaNt Chemotherapy and Physical Exercise in Stage III Colon Cancer (iMAGINE): a Prospective, Randomized, Open-label, Multicenter, Phase III Clinical Trial

The overall aim of this study is to prospectively validate the superiority of the Immunoscore as a decision guidance for adjuvant chemotherapy in stage III colon cancer patients, in comparison to the conventional TNM-based high- or low-risk classification.

Study Overview

• Status: Not yet recruiting
• Conditions: Colon Cancer Stage III
• Intervention / Treatment: Drug: Capecitabine; Drug: Oxaliplatin; Drug: Fluorouracil; Drug: Leucovorin; Device: Immunoscore® assay; Other: Physical exercise

• Study Type: Interventional
• Enrollment (Estimated): 1638
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Johannes Laengle, MD, PhD; Phone Number: +43 1 40400 69260; Email: johannes.laengle@meduniwien.ac.at
• Study Contact Backup: Name: Michael Bergmann, MD; Phone Number: +43 1 40400 69260; Email: michael.bergmann@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna
    • Contact: Johannes Laengle, MD, PhD; Phone Number: +43 1 40400 69260; Email: johannes.laengle@meduniwien.ac.at
    • Sub-Investigator: Johannes Laengle, MD, PhD
    • Principal Investigator: Michael Bergmann, MD
    • Contact: Michale Bergmann, MD; Phone Number: +43 1 40400 69260; Email: michael.bergmann@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18-75 years of age
• All sexes
• Histologically confirmed stage III carcinoma of the colon
• Medical need for an adjuvant chemotherapy
• Suitable to withstand the course of an adjuvant chemotherapy
• Written informed consent form (ICF) for participation in the study
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

• Neoadjuvant treatment
• Metastatic disease
• Pregnancy, breastfeeding or expectancy to conceive
• Disagreement of participants with reproductive potential to use contraception throughout the study period and for up to 180 days after the last dose of study therapy
• Uncontrolled or significant cardiovascular disease (myocardial infarction, uncontrolled angina, any history of clinically significant arrhythmias, QTc prolongation in males > 450 ms and > 470 ms in females, participants with history of myocarditis)
• Hepatitis B or C
• Human immunodeficiency virus (HIV)
• Immunodeficiency
• Allogeneic tissue or solid organ transplantation
• Systemic steroids or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
• Diagnosed and/or treated additional malignancy within 5 years of randomization, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin and/or curatively-resected in situ cervical and/or breast cancers
• Participants with serious or uncontrolled medical disorders
• Allergies and adverse drug reaction (history of allergy or hypersensitivity to study drug components, contraindications to any of the study drugs of the chemotherapy regimen)
• Other exclusion criteria: Prisoners or participants who are involuntarily incarcerated, participants who are compulsorily detained for treatment of either a psychiatric or physical (i.e. infectious disease) illness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immunoscore stratification; Immunoscore low (I-Low; I0-1): 3 months CAPOX (oxaliplatin 130 mg/m2 IV over 2 h and capecitabine 1000 mg/m2 PO twice daily (days 1-14). 21-day treatment cycle.). Concomitantly, standardised physical excise (stair walking excise twice a week for 12 weeks), which will be monitored by an electronic sports device.; Immunoscore intermediate-high (I-IntHi; I2-3): 6 months FOLFOX (oxaliplatin 85 mg/m2 IV (on day 1) and folinic acid 200 mg/m2 IV over 2 h, followed by a bolus of fluorouracil 400 mg/m2 IV over 2-4 min, followed by fluorouracil 600 mg/m2 IV over 22 h (for 2 consecutive days). 14-day treatment cycle.); Immunoscore high (I high; I4): no adjuvant treatment.	Drug: Capecitabine; Tablet; Drug: Oxaliplatin; Infusion; Drug: Fluorouracil; Infusion; Drug: Leucovorin; Infusion; Device: Immunoscore® assay; Whole-slide tissue analysis of CD3+ and cytotoxic CD8+ T cells in the tumor and in the invasive margin; Other: Physical exercise; Increasing stair walking exercise twice a week over 12 weeks total.
Active Comparator: TNM stratification; TNM-based low-risk (pT1, pT2 or pT3 and pN1): 3 months CAPOX (oxaliplatin 130 mg/m2 IV over 2 h and capecitabine 1000 mg/m2 PO twice daily (days 1-14). 21-day treatment cycle.); TNM-based high-risk (pT4 and/or pN2): 6 months FOLFOX (oxaliplatin 85 mg/m2 IV (on day 1) and folinic acid 200 mg/m2 IV over 2 h, followed by a bolus of fluorouracil 400 mg/m2 IV over 2-4 min, followed by fluorouracil 600 mg/m2 IV over 22 h (for 2 consecutive days). 14-day treatment cycle.)	Drug: Capecitabine; Tablet; Drug: Oxaliplatin; Infusion; Drug: Fluorouracil; Infusion; Drug: Leucovorin; Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival (DFS)	Impact of Immunoscore stratification on DFS at 3 years (time from surgery to first observation of disease recurrence or death due to any cause)	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Impact of Immunoscore stratification on OS at 3 years (time from surgery to death due to any cause)	3 years
Time to recurrence (TTR)	Impact of Immunoscore stratification on TTR at 3 years (time from surgery to disease recurrence)	3 years
Treatment-related adverse events (AE)	Impact of Immunoscore stratification on treatment-related AEs assessed according to the latest Common Terminology Criteria of Adverse Events (CTCAE).	3 years
Cost analysis	Impact of Immunoscore stratification on treatment-related costs, assessed by cost-effectiveness analysis (CEA) according to the latest Good Research Practices for Cost-Effectiveness Analysis Alongside Clinical Trials of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR).	3 years
Health-related quality of life (HRQOL)	Impact of Immunoscore stratification on quality of life assessed by the latest version of the European Organization for Research and Treatment of Cancer (EORCT) Quality of Life Group (QLG) questionnaires C30 and CR29.	3 years

Collaborators and Investigators

• Sponsor: Johannes Laengle, MD, PhD
• Investigators: Principal Investigator: Jérôme Galon, PhD, Laboratory of Integrative Cancer Immunology, INSERM, Cordeliers Research Center

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: July 21, 2020
• First Submitted That Met QC Criteria: July 23, 2020
• First Posted (Actual): July 27, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Physical exercise; FOLFOX; Colon cancer; CAPOX; Immunoscore
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Capecitabine; Oxaliplatin; Leucovorin
• Other Study ID Numbers: iMAGINE; 2020-000401-91 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No