RecruitingPhase 2NCT04503694

Neoadjuvant Regorafenib in Combination with Nivolumab and Short-course Radiotherapy in Stage II-III Rectal Cancer

A Phase II Trial of Neoadjuvant Regorafenib in Combination with Nivolumab and Short-course Radiotherapy in Stage II-III Rectal Cancer

Sponsor

Jules Bordet Institute

Enrollment

72 participants

Start Date

Mar 25, 2021

Study Type

INTERVENTIONAL

Conditions

Rectal Cancer Stage II Rectal Cancer Stage III

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(or watch \& wait approach). 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 treatment: This consists of treatment with nivolumab (240 mg intravenously, on day 1 and 15) and regorafenib (60 mg/day orally, from day 1 to 14) * Standard SCRT: This consists of 25 Gy delivered in 5 fractions (from day 22 to 26) * Consolidation treatment: This consists of treatment with nivolumab (240 mg intravenously, on day 29, 43 and 57) and regorafenib (60 mg/day orally, from day 29 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). As an alternative to surgery, subjects who achieve cCR can be offered a watch \& wait approach. * 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.

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study tests whether combining an immunotherapy drug (nivolumab), a targeted drug (regorafenib), and short-course radiation therapy before surgery improves outcomes in people with stage II or III rectal cancer. **You may be eligible if...** - You are 18 or older - You have confirmed stage II or III rectal cancer (adenocarcinoma) - Your tumor is located in the lower part of the rectum, within 15 cm of the anal opening - You are in good enough health to tolerate surgery and chemotherapy (ECOG performance status 0–1) - You do not have cancer spread to distant organs **You may NOT be eligible if...** - Your cancer has already spread to other organs (metastatic disease) - You have had prior radiation to the pelvis - You have active autoimmune disease or inflammatory bowel disease - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

PROCEDURESurgery

Subject will undergo surgical resection of the primary tumour in the rectum between day 74 and 87. Surgery must be performed according to the principles of total mesorectal excision as described by Heald et al. The type of surgical approach (low anterior resection or abdominoperineal resection, etc.) will be left to the discretion of the treating surgeon.

DRUGNivolumab 10 MG/ML Intravenous Solution

Nivolumab will be given at a dose of 240 mg during the pre-operative phase only as indicated below: * On day 1 and 15, during the "Induction treatment" * On day 29, 43 and 57, during the "Consolidation treatment"

DRUGRegorafenib 30 MG Oral Tablet

Regorafenib will be administered orally once a day at a dose of 60 mg/day (2 tablets of 40 mg), during the pre-operative phase only as indicated below: * From day 1 to 14, during the "Induction treatment" * From day 29 to 49, during the "Consolidation treatment"

RADIATIONRadiotherapy

All study subjects will receive 5 daily fractions of radiotherapy. Each fraction will consist of 5 Gy for a total dose of 25 Gy. Radiotherapy is to start on day 22 and to finish on day 26.

PROCEDURENon-operative Management

Subjects who achieve cCR after pre-operative treatment can, after discussion with the local investigator, decline surgery and opt for a non-operative management. cCR will need to be confirmed between day 67 and 74 by the following procedures per local practise: * Digital rectal examination * Rectal endoscopy * Rectal MRI Subjects who achieve near cCR at the first assessment time point after pre-operative treatment, can be re-assessed 6 to 8 weeks later with the same procedures. If cCR is diagnosed, they can opt for watch \& wait, otherwise they would need to undergo surgical resection. Subjects who opt for a non-operative management will be followed for tumour recurrence and survival for 5 years after end of treatment visit. Follow-up for these subjects will be more intensive than that for subjects undergoing surgery