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

NCT03608046

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.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
AvelumabAvelumab, Cetuximab, Irinotecan
Cetuximab InjectionAvelumab, Cetuximab, Irinotecan
IrinotecanAvelumab, 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

NameTypeDescriptionInterventions
Avelumab, Cetuximab, IrinotecanExperimentalAvelumab : 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:Not yet recruiting
Lead Sponsor:Cliniques universitaires Saint-Luc- Université Catholique de Louvain

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