Actively Recruiting
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
Led by Centre Hospitalier Universitaire Dijon · Updated on 2025-02-18
68
Participants Needed
1
Research Sites
290 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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
Official Title
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
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 65 18 years
- Histologically confirmed rectal adenocarcinoma with mismatch-repair deficiency (dMMR) or microsatellite instability-high (MSI-H) determined by IHC and PCR or NGS
- Stage II or III middle or lower third rectal adenocarcinoma diagnosed by clinical and MRI criteria
- WHO performance status of 0 or 1
- Adequate liver function: AST and ALT 64 5 x upper normal limit, total bilirubin 64 35 bcM/L, albumin 5 28 g/L, Child-Pugh A if cirrhosis present
- Adequate blood and kidney function: hemoglobin > 9 g/dl, platelets > 100 G/L, ANC 65 1.5 G/L, creatinine clearance 65 40 ml/min
- Women of childbearing potential agree to use contraception during treatment and for 4 months after
- Men with partners of childbearing potential agree to use contraception during treatment and for 4 months after
- Ability to understand and sign informed consent prior to screening
- Affiliated with a social security scheme
You will not qualify if you...
- Stage IV or upper third rectal adenocarcinoma (above 10 cm from anal verge or supraperitoneal)
- Prior immunotherapy, chemotherapy, or radiotherapy for rectal cancer
- Persistent treatment-related toxicities greater than grade 1
- Active infection requiring systemic therapy within 1 week before first study dose
- Contraindication to pelvic radiotherapy
- Hypersensitivity to dostarlimab or its components
- Allergy to Chinese hamster ovary cell components
- History of severe or life-threatening autoimmune disease
- Uncontrolled or symptomatic cardiac disease
- Interstitial lung disease
- Uncontrolled CNS metastases or carcinomatous meningitis
- Positive hepatitis B surface antigen or core antibody at screening or within 3 months
- Positive hepatitis C antibody or RNA test at screening or within 3 months
- Known HIV infection
- Live vaccinations within 14 days before treatment start
- Immunosuppression requiring systemic corticosteroids >10 mg/day prednisone equivalent
- Active autoimmune disease needing systemic treatment in past 2 years or immunosuppressive therapy in past 7 days
- History of organ transplantation
- Pregnant or breastfeeding women
- Prior severe immune-related adverse events with immunotherapy
- Unstable progressive diseases in last 6 months (hepatic, renal, respiratory insufficiency)
- Other cancers treated within 5 years except certain cured cancers
- Major surgery within 4 weeks before inclusion
- Legal incapacity or unable to consent
- Conditions that may impair study compliance or follow-up
AI-Screening
AI-Powered Screening
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Trial Site Locations
Total: 1 location
1
CHU Dijon Bourgogne
Dijon, France, 21000
Actively Recruiting
Research Team
A
Antoine KAROUI
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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