Back to resultsAvelumab Combined With Cetuximab and Irinotecan for Treatment Refractory Metastatic Colorectal Microsatellite Stable Cancer (AVETUXIRI)
Primary Purpose
Colorectal Neoplasms, Malignant
Status
Recruiting
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
Avelumab
Cetuximab Injection
Irinotecan
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Neoplasms, Malignant
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.
Sites / Locations
- Cliniques Universitaires Saint-LucRecruiting
- Grand Hôpital de CharleroiRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Avelumab, Cetuximab, Irinotecan
Arm Description
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).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Adverse events
Safety will be controlled
Full Information
NCT ID
NCT03608046
First Posted
July 16, 2018
Last Updated
October 20, 2020
Sponsor
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
1. Study Identification
Unique Protocol Identification Number
NCT03608046
Brief Title
Avelumab Combined With Cetuximab and Irinotecan for Treatment Refractory Metastatic Colorectal Microsatellite Stable Cancer
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Recruiting
Study Start Date
October 3, 2018 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasms, Malignant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
59 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Avelumab, Cetuximab, Irinotecan
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Avelumab
Intervention Description
Avelumab will be administered at a fixed dose of 10 mg/kg once every 2- week
Intervention Type
Drug
Intervention Name(s)
Cetuximab Injection
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Description
Irinotecan will be administered every 2 weeks (180 mg/m2)
Primary Outcome Measure Information:
Title
Tumor response rate
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.
Time Frame
Up to 19 weeks
Secondary Outcome Measure Information:
Title
Adverse events
Description
Safety will be controlled
Time Frame
Up to 19 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marc Van Den Eynde, MD, PhD
Phone
00323 764
Ext
1041
Email
marc.vandeneynde@uclouvain.be
Facility Information:
Facility Name
Cliniques Universitaires Saint-Luc
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marc Van Den Eynde, MD, PhD
Phone
0032 2 764
Ext
1041
Email
marc.vandeneynde@uclouvain.be
First Name & Middle Initial & Last Name & Degree
Marie-Laure Castella, Study coordinator
Phone
0032 2 764
Ext
5427
Email
marie-laure.castella@uclouvain.be
Facility Name
Grand Hôpital de Charleroi
City
Charleroi
ZIP/Postal Code
6000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Javier Carrasco, MD, PhD
Phone
0032 2 71 10
Ext
20 20
Email
javier.carrasco@ghdc.be
12. IPD Sharing Statement
Learn more about this trial
Avelumab Combined With Cetuximab and Irinotecan for Treatment Refractory Metastatic Colorectal Microsatellite Stable Cancer
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