Avelumab Combined With Cetuximab and Irinotecan for Treatment Refractory Metastatic Colorectal Microsatellite Stable Cancer

NCT03608046 | Unknown Phase 2

• 1 other identifier: UCL-mCRC-2018-MS100070-0095
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 2

Brief Summary

Cancer immunotherapy with immunostimulatory antibodies targeting the CTLA-4 or PD-1/PD-L1 pathways has demonstrated its efficacy in variable proportions of cancer. For metastatic colorectal cancer (mCRC) it appeared that only the small subgroup of patients with MSI-H tumors (microsatellite instability-high phenotype) had a clinically meaningful response to the anti-PD-1- L1 antibodies. In the majority group of non-MSI-H CRC (90-95% of patients), current research expect that additional means would be able to render the tumor "immunogenic" (like MSI-H CRC) and increase the intratumoral immune infiltrate which is the prerequisite to observe a benefit from PD1-PD-L1 inhibitors. Combinations of immune checkpoint inhibitors and procedures that increase intratumoral immune responses, such as targeted therapy, are actively explored.

Conditions

Colorectal Neoplasms, Malignant

Outcome Measures

Primary Outcomes (1)

• Tumor response rate

  The overall tumor response rate (ORR) defined as the proportion of all included patient with a confirmed best overall tumor response of PR or CR according to irRECIST 1.1 occuring until 19 weeks after study treatment start.

  Up to 19 weeks

Secondary Outcomes (1)

• Adverse events

  Up to 19 weeks

Study Arms (1)

Avelumab, Cetuximab, Irinotecan

EXPERIMENTAL

Avelumab : administrated at a fixed dose of 10 mg/kg once every 2- week. Cetuximab: administered at 400 mg/m2 loading dose week 1, 250 mg/m2 from week 2 followed by 500 mg/m2 from week 3. Irinotecan: administrated every 2 weeks (180 mg/m2).

Drug: Avelumab; Drug: Cetuximab Injection; Drug: Irinotecan

Interventions

Avelumab DRUG

Avelumab will be administered at a fixed dose of 10 mg/kg once every 2- week

Avelumab, Cetuximab, Irinotecan

Cetuximab Injection DRUG

Cetuximab will be administered at 400 mg/m2 loading dose week 1, 250 mg/m2 from week 2 followed by 500 mg/m2 from week 3 and irinotecan administered every 2 weeks (180 mg/m2).

Avelumab, Cetuximab, Irinotecan

Irinotecan DRUG

Irinotecan will be administered every 2 weeks (180 mg/m2)

Avelumab, Cetuximab, Irinotecan

Eligibility Criteria

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

You may qualify if:

• Age 18 and over, Performance status: ECOG 0-1
• Histologically proven metastatic colorectal adenocarcinoma, refractory to standard chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan) and anti-EGFR treatment (only for RAS WT tumor)
• Measurable disease (RECIST 1.1)
• Metastasis accessible for sequential biopsies
• Patient consent for metastasis biopsies in the study protocol
• BRAF V600E wild-type and MSS tumors
• Adequate normal organ and marrow function (see adequate section of the full protocol for definition)
• Life expectancy of at least 4 months

You may not qualify if:

• Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy that are not indicated in the study protocol
• Systemic autoimmune disease,
• Chronic treatment with corticoids or other immunosuppressive treatment
• Clinically significant cardiac, lung or general disease despite optimal treatment
• Non-progressive disease following irinotecan-based treatment.
• For RAS WT, non-progressive disease following anti-EGFR treatment.

Sponsors & Collaborators

• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: lead

Study Sites (2)

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

RECRUITING

Grand Hôpital de Charleroi

Charleroi, 6000, Belgium

RECRUITING

Related Publications (1)

• Huyghe N, Benidovskaya E, Masoodi T, Sinapi I, De Cuyper A, Vempalli F, Beyaert S, Bouzin C, Osorio FM, Ferraro L, van Baren N, Helaers R, Goffette P, Ghaye B, van Maanen A, Castella ML, Ceccarelli M, Bedognetti D, Galon J, Hendrickx WRL, Carrasco J, Van den Eynde M. Impact of the tumor immune contexture in microsatellite-stable metastatic colorectal cancer treated with avelumab, cetuximab, and irinotecan. Cell Rep Med. 2025 Jul 15;6(7):102201. doi: 10.1016/j.xcrm.2025.102201. Epub 2025 Jun 24.

  PMID: 40562041 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

avelumab; Cetuximab; Irinotecan

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Central Study Contacts

Marc Van Den Eynde, MD, PhD

CONTACT

00323 764; marc.vandeneynde@uclouvain.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2018
• First Posted: July 31, 2018
• Study Start: October 3, 2018
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: October 22, 2020

Record last verified: 2020-10

Locations

BE (2)