NCT04072198

Nivolumab Plus FOLFOXIRI/Bevacizumab in First Line Chemotherapy of Advanced Colorectal Cancer RASm/BRAFm Patients

Phase II Study on NIVolumab in Combination With FOLFOXIRI/Bevacizumab in First Line Chemotherapy of Advanced COloRectal Cancer RASm/BRAFm Patients

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 73 (actual)
• Sponsor: Gruppo Oncologico Italiano di Ricerca Clinica · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a multicentric single arm, open label trial. In this study patients candidated to a first line of chemotherapy for metastatic colorectal cancer will be treated with 8 cycles of folfoxiri plus bevacizumab plus nivolumab followed by a maintenance with bevacizumab plus nivolumab. Patients who do not progress during chemotherapy phase will receive bevacizumab plus nivolumab as maintenance therapy. Patients will be treated until disease progression, unacceptable toxicity or patient/physician decision.

Detailed description

This is a prospective, open-label, multicentric phase II trial in which patients with metastatic colorectal cancer RASm/BRAFm patients will receive nivolumab in combination with FOLFOXIRI/Bevacizumab as first line chemotherapy. Study screening will take place within 28 days prior to initiation of study treatment. At screening, every patient must have local RAS/BRAF known status. A centralized review of RAS/BRAF status will be performed during the study. Eligible patients will be enrolled and begin treatment with FOLFOXIRI/bevacizumab plus nivolumab every 2 weeks for 8 cycles followed by maintenance with bevacizumab plus nivolumab every 2 weeks until disease progression, unacceptable toxicity or patient/physician decision. Bevacizumab will be administered intravenously at dose of 5 mg/kg every 2 weeks. Nivolumab will be administered intravenously at flat dose of 240 mg every 2 weeks. Folfoxiri will be administered as 165 mg/m2 intravenous infusion of irinotecan for 60 min, followed by an 85 mg/m2 intravenous infusion of oxaliplatin given concurrently with leucovorin at a dose of 200 mg/m2 for 120 min, followed by a 3200 mg/m2 continuous infusion of fluorouracil for 48 h. During the study treatment period, patients will be followed for safety based on AE assessments including vital signs, physical findings and clinical laboratory test results. In order to guarantee the safety of the patients, the enrolment will be stopped when the 10th patient will start treatment. An Independent Monitoring Committee will evaluate the safety data of these patients and will decide if the study should be completed, amended or closed. Efficacy will be evaluated by the investigator according to RECIST v1.1 every 8 weeks during treatment and then every 3 months for 3 years. During the study baseline tumor blocks will be centrally analysed to determinate inflammatory infiltrate, MSI/MSS and PD-L1 status. The biological characterization and Tumor Mutation Burden (TMB) will be also analysed centrally. Following discontinuation of study treatment, safety assessments will be conducted 30 days after the last study drug administration or until initiation of other anti-cancer therapy (whichever occurs first). Thereafter, patients will be followed for disease progression (unless this has already occurred), SAEs, anticancer therapy and survival. Follow-up will continue for up to 3 years. A blood sample will be collected for all patients at baseline, prior to cycle 5, at the end of chemotherapy and at disease progression. Quality of life will be assessed at baseline, every 4 weeks during treatment and study discontinuation visit.

Conditions

• Colorectal Cancer

Interventions

Type	Name	Description
DRUG	Nivolumab	240 mg every 2 weeks for 8 cycles followed by maintenance
DRUG	Bevacizumab	5 mg/kg every 2 weeks for 8 cycles followed by maintenance
DRUG	Irinotecan	165 mg/m2 every 2 weeks for 8 cycles
DRUG	Oxaliplatin	85 mg/m2 every 2 weeks for 8 cycles
DRUG	Leucovorin	200 mg/m2 every 2 weeks for 8 cycles
DRUG	fluoruracil	3200mg/m2 every 2 weeks for 8 cycles

Timeline

• Start date: 2019-09-26
• Primary completion: 2024-08-30
• Completion: 2024-10-30
• First posted: 2019-08-28
• Last updated: 2025-03-13

Locations

8 sites across 1 country: Italy