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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

NCT06762405 · Status: RECRUITING · Phase: PHASE3 · Type: INTERVENTIONAL · Enrollment: 68

Last updated 2025-02-18

No results posted yet for this study

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

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

Sponsors & Collaborators

  • Centre Hospitalier Universitaire Dijon

    lead OTHER

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2025-02-06
Primary Completion
2030-09-30
Completion
2030-09-30

Countries

  • France

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06762405 on ClinicalTrials.gov