Immunoscore As Decision Guidance for Adjuvant Chemotherapy in Colon Cancer

NCT04488159 | Withdrawn Phase 3 DMC

• 2 other identifiers: iMAGINE2020-000401-91
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colon Cancer Stage III

Keywords

Colon cancer; Immunoscore; CAPOX; FOLFOX; Physical exercise

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Overall survival (OS)

  3 years

• Time to recurrence (TTR)

  3 years

• Treatment-related adverse events (AE)

  3 years

• Health-related quality of life (HRQOL)

  3 years

• Cost analysis

  3 years

Study Arms (2)

Immunoscore stratification

EXPERIMENTAL

* 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; Drug: Oxaliplatin; Drug: Fluorouracil; Drug: Leucovorin; Device: Immunoscore® assay; Other: Physical exercise

TNM stratification

ACTIVE COMPARATOR

* 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; Drug: Oxaliplatin; Drug: Fluorouracil; Drug: Leucovorin

Interventions

Capecitabine DRUG

Tablet

Immunoscore stratification; TNM stratification

Oxaliplatin DRUG

Infusion

Immunoscore stratification; TNM stratification

Fluorouracil DRUG

Infusion

Immunoscore stratification; TNM stratification

Leucovorin DRUG

Infusion

Immunoscore stratification; TNM stratification

Immunoscore® assay DEVICE

Whole-slide tissue analysis of CD3+ and cytotoxic CD8+ T cells in the tumor and in the invasive margin

Immunoscore stratification

Physical exercise OTHER

Increasing stair walking exercise twice a week over 12 weeks total.

Immunoscore stratification

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Johannes Laengle, MD, PhD: lead

Study Sites (1)

Medical University of Vienna

Vienna, Vienna, 1090, Austria

Location

MeSH Terms

Conditions

Colonic Neoplasms; Motor Activity

Interventions

Capecitabine; Oxaliplatin; Fluorouracil; Leucovorin; Exercise

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Behavior

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Jérôme Galon, PhD

  Laboratory of Integrative Cancer Immunology, INSERM, Cordeliers Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: July 21, 2020
• First Posted: July 27, 2020
• Study Start: December 1, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: September 20, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)