Neoadjuvant Regorafenib in Combination With Nivolumab and Short-course Radiotherapy in Intermediate-risk, Stage II-III Rectal Cancer

• Status: Recruiting
• Trial end date: 2028-09-01

Summary

This is a multicenter, single-arm, phase II study of nivolumab in combination with regorafenib in subjects with locally-advanced rectal cancer who are eligible for a curative treatment including pre-operative SCRT and TME. The study is based on the Simon's two-stage design and a maximum of 60 subjects will be enrolled. In addition to the standard efficacy interim analysis according to the statistical design, a safety interim analysis will be performed on the first 6 subjects who have completed the study treatment to ensure safe continuation of the study investigation.

Eligible subjects will be treated according to the following sequential treatment plan:

• Induction systemic period 1: This consists of treatment with nivolumab (240 mg intravenously, on day 1 and 14) and regorafenib (80 mg/day orally, from day 1 to 14)

• Standard SCRT: This consists of 25 Gy delivered in 5 fractions (from day 21 to 25)

• Induction systemic period 2: This consists of treatment with nivolumab (240 mg intravenously, on day 28, 42 and 56) and regorafenib (80 mg/day orally, from day 28 to 49)

• Surgery: Surgical resection will be performed according to the principles of TME (between day 74 and 87, i.e., between 7 to 8 weeks after completion of SCRT)

• Adjuvant chemotherapy: Administration of adjuvant chemotherapy will be left to the discretion of the treating physician

The study also includes translational procedures (i.e. collection of tumour biopsies, blood samples and stool samples at pre-specified time points) for exploratory molecular and immune contexture analyses. These are mandatory for all study subjects.

• Phase: Phase 2

Details

• Lead Sponsor: Jules Bordet Institute
• Treatments: Nivolumab