Avelumab Combined With Cetuximab and Irinotecan for Treatment Refractory Metastatic Colorectal Microsatellite Stable Cancer
- Conditions
- Colorectal Neoplasms, Malignant
- Interventions
- Registration Number
- NCT03608046
- Lead Sponsor
- Cliniques universitaires Saint-Luc- Université Catholique de Louvain
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 59
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Avelumab, Cetuximab, Irinotecan Cetuximab Injection 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, Irinotecan Avelumab 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, Irinotecan Irinotecan 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).
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Adverse events Up to 19 weeks Safety will be controlled
Trial Locations
- Locations (2)
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
Grand Hôpital de Charleroi
🇧🇪Charleroi, Belgium