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

Colorectal Neoplasms, Malignant Clinical Trial

— AVETUXIRI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03608046
• Other study ID #: UCL-mCRC-2018-MS100070-0095
• Status: Recruiting
• Phase: Phase 2
• Start date: October 3, 2018
• Est. completion date: December 31, 2023

Study information

• Verified date: October 2020
• Source: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Contact: Marc Van Den Eynde, MD, PhD
• Phone: 00323 764
• Email: marc.vandeneynde[@]uclouvain.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 59
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Colorectal Neoplasms, Malignant
• Neoplasms

Intervention

Drug:
• Avelumab
Avelumab will be administered at a fixed dose of 10 mg/kg once every 2- week
• 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).
• Irinotecan
Irinotecan will be administered every 2 weeks (180 mg/m2)

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Grand Hôpital de Charleroi	Charleroi

Sponsors (1)

Lead Sponsor	Collaborator
Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Adverse events	Safety will be controlled	Up to 19 weeks