NCT06762405

PRODIGE 90 - (FFCD 2204) Neoadjuvant Dostarlimab with Short Course Radiotherapy in a Watch-and-wait Strategy for Microsatellite Unstable or Mismatch Repair-deficient Locally Advanced Rectal Cancer Patients

PRODIGE 90 - (FFCD 2204) - PREDIR-NEOREC Neoadjuvant Dostarlimab with Short Course Radiotherapy in a Watch-and-wait Strategy for Microsatellite Unstable or Mismatch Repair-deficient Locally Advanced Rectal Cancer Patients: a Randomized Phase II Trial Phase II Randomized Study Non-comparative - Multicenter

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 68 (estimated)
• Sponsor: Centre Hospitalier Universitaire Dijon · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Total neoadjuvant treatment (TNT) including radiotherapy and induction or consolidation systemic chemotherapy has become the standard treatment for patients with stage II and III rectal adenocarcinoma. Along with the improvement of DFS, this preoperative treatment has paved the way to a paradigm-shifting nonoperative management. Indeed, rectal preservation has become a new goal for patients without detectable residual cancer after TNT with the option to reserve surgery for those with cancer regrowth (25-40%). Five to 10% of non-metastatic rectal cancer patients are molecularly characterized as microsatellite unstable (MSI) or mismatch repair-deficient (dMMR), and present a decreased response to systemic chemotherapy. As this tumor phenotype is associated with high immunogenicity, immunotherapy with anti-PD1 molecules has recently emerged as the new standard first line treatment in the metastatic setting, with long duration of cancer control for at least 40% of patients. In patients with localized rectal tumors, it has been suggested that immunotherapy alone may induce complete clinical response and may allow these patients to be considered for nonoperative therapeutic approaches. Finally, given the efficacy of immunotherapy in MSI rectal patients, we did not want to differ for 5 weeks this treatment with the risk of disease progression by given long-course RT. In the present trial, radiotherapy is evaluated as a " potentiating " treatment for immunotherapy rather than as a " local treatment " in a TNT strategy.

Conditions

• Rectal Adenocarcinoma with Mismatch-repair Deficient (dMMR)/ Microsatellite Instability-high (MSI-H)

Interventions

Type	Name	Description
RADIATION	radiotherapy	short course of radiotherapy (5 grays × 5 days)
DRUG	Dostarlimab	dostarlimab 500 mg intravenous infusion every 3 weeks for 6 months (nine cycles)
BIOLOGICAL	Biological study on circulating tumor DNA (optional for the patient)	* Tissue collection (3 time points: baseline, w12 and 25) for: * Exome (on tumor and normal tissue), * 3'RNAseq, * Hiplex Immunofluorescence * In addition, 48 patients will be tested for Spatial transcriptomics assuming that 24 patients may have non-complete response and/or local recurrence and/or metastatic recurrence and will be paired with 24 patients with complete response and free of any disease at 2 years. * Blood collection (5 time points: baseline, w3, 6, 12 and 24) for: * ctDNA * Cytokine dosage * Proteomic analyses * Stool collection (3 time points: baseline, w3 and 24) for: Microbiota analyses

Timeline

• Start date: 2025-02-06
• Primary completion: 2030-09-01
• Completion: 2030-09-01
• First posted: 2025-01-07
• Last updated: 2025-02-18

Locations

1 site across 1 country: France