Colorectal Neoplasms, Malignant
Conditions
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.
Interventions
DRUGAvelumab
Avelumab will be administered at a fixed dose of 10 mg/kg once every 2- week
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).
DRUGIrinotecan
Irinotecan will be administered every 2 weeks (180 mg/m2)
Sponsors
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor response rate | Up to 19 weeks | 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
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | Up to 19 weeks | Safety will be controlled |
Countries
Belgium
Contacts
Primary ContactMarc Van Den Eynde, MD, PhD
Outcome results
None listed