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

Avelumab Combined With Cetuximab and Irinotecan for Treatment Refractory Metastatic Colorectal Microsatellite Stable Cancer - A Proof of Concept, Open Label Non-randomized Phase IIa Study. The AVETUXIRI Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Neoplasms, Malignant
• Intervention / Treatment: Drug: Avelumab; Drug: Cetuximab Injection; Drug: Irinotecan

• Study Type: Interventional
• Enrollment (Anticipated): 59
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Marc Van Den Eynde, MD, PhD; Phone Number: 1041 00323 764; Email: marc.vandeneynde@uclouvain.be

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Recruiting
    • Cliniques universitaires Saint-Luc
    • Contact: Marc Van Den Eynde, MD, PhD; Phone Number: 1041 0032 2 764; Email: marc.vandeneynde@uclouvain.be
    • Contact: Marie-Laure Castella, Study coordinator; Phone Number: 5427 0032 2 764; Email: marie-laure.castella@uclouvain.be
  • Charleroi, Belgium, 6000
    • Recruiting
    • Grand Hôpital de Charleroi
    • Contact: Javier Carrasco, MD, PhD; Phone Number: 20 20 0032 2 71 10; Email: javier.carrasco@ghdc.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 98 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Avelumab, Cetuximab, Irinotecan; 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; Avelumab will be administered at a fixed dose of 10 mg/kg once every 2- week; Drug: Cetuximab Injection; 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).; Drug: Irinotecan; Irinotecan will be administered every 2 weeks (180 mg/m2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Safety will be controlled	Up to 19 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2018
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: July 16, 2018
• First Submitted That Met QC Criteria: July 27, 2018
• First Posted (Actual): July 31, 2018

Study Record Updates

• Last Update Posted (Actual): October 22, 2020
• Last Update Submitted That Met QC Criteria: October 20, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Topoisomerase I Inhibitors; Irinotecan; Avelumab; Cetuximab
• Other Study ID Numbers: UCL-mCRC-2018-MS100070-0095

Drug and device information, study documents

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