Description:
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.
Title
- Brief Title: Avelumab Combined With Cetuximab and Irinotecan for Treatment Refractory Metastatic Colorectal Microsatellite Stable Cancer
- 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 IDs
- ORG STUDY ID:
UCL-mCRC-2018-MS100070-0095
- NCT ID:
NCT03608046
Conditions
- Colorectal Neoplasms, Malignant
Interventions
| Drug | Synonyms | Arms |
|---|
| Avelumab | | Avelumab, Cetuximab, Irinotecan |
| Cetuximab Injection | | Avelumab, Cetuximab, Irinotecan |
| Irinotecan | | Avelumab, Cetuximab, Irinotecan |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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). | - Avelumab
- Cetuximab Injection
- Irinotecan
|
Eligibility Criteria
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.
| Maximum Eligible Age: | 100 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Tumor response rate |
| Time Frame: | Up to 19 weeks |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | Adverse events |
| Time Frame: | Up to 19 weeks |
| Safety Issue: | |
| Description: | Safety will be controlled |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Cliniques universitaires Saint-Luc- Université Catholique de Louvain |
Last Updated
October 22, 2020
