Neoadjuvant immunotherapy and radiotherapy for advanced rectal cancer
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
This study is testing if combining a new immunotherapy drug with short radiation treatment can help people with advanced rectal cancer avoid surgery and improve their chances of staying cancer-free.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 68 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Centre Hospitalier Universitaire Dijon Academic / other |
| Drugs / interventions | dostarlimab, chemotherapy, immunotherapy, prednisone |
| Locations | 1 site (Dijon) |
| Trial ID | NCT06762405 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the combination of neoadjuvant immunotherapy using Dostarlimab and short-course radiotherapy for patients with locally advanced rectal cancer characterized by microsatellite instability-high or mismatch repair deficiency. The approach aims to achieve a watch-and-wait strategy, allowing for rectal preservation in patients who show no detectable residual cancer after treatment. The study focuses on patients with stage II and III rectal adenocarcinoma, assessing the effectiveness of this treatment regimen in improving disease-free survival and reducing the need for surgery. The trial also includes an optional biological study on circulating tumor DNA.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed locally advanced rectal adenocarcinoma that is microsatellite unstable or mismatch repair deficient.
Not a fit: Patients with metastatic rectal cancer or those with other types of rectal cancer that do not exhibit dMMR or MSI-H characteristics may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly improve treatment outcomes and quality of life for patients by reducing the need for surgery.
How similar studies have performed: Other studies have shown promising results with similar immunotherapy approaches in treating rectal cancer, indicating potential for success in this trial.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Age ≥18 years * Histologically proven rectal adenocarcinoma with Mismatch-repair Deficient (dMMR)/ microsatellite instability-high (MSI-H). Tumour status (dMMR/MSI-H) should be determined using both IHC (Immunohistochemistry) and PCR (polymerase chain reaction) or NGS (Next-Generation sequencing) * Stage II or III and middle and lower third rectal adenocarcinoma (diagnosed on the basis of standard clinical and MRI criteria) * WHO performance status 0 or 1 * Adequate liver function: AST and ALT ≤ 5 x ULN (upper normal limit), total bilirubin ≤ 35 μM/L, albumin ≥ 28 g/L and Child-Pugh A score (if cirrhosis associated) * Adequate hematological and renal function (hemoglobin \> 9 g/dl, platelets \> 100 G/L, ANC ≥ 1.5 G/L) and renal function (creatinine clearance ≥ 40ml/min according to MDRD formula) * Women of childbearing potential must agree to use contraception during the trial treatment and for at least 4 months after discontinuation of the experimental treatments. Men who have sex with women of childbearing potential must agree to use contraception during treatment and for at least 4 months after discontinuation of the experimental treatments * Ability of patient to understand, sign and date the informed consent form before any study specific screening procedures * Patient affiliated to a social security scheme Exclusion Criteria: * Stage IV and upper third rectal adenocarcinoma (above 10 cm from the anal verge or sus-peritoneal on standard clinical and MRI criteria) * Patients who have already received immunotherapy, chemotherapy or radiotherapy for rectal cancer * Persistent toxicities related to prior treatment of grade greater than 1 * Participant has an active infection requiring systemic therapy within 1 week prior to the anticipated first dose of study treatment * Contraindication to pelvic radiotherapy * Hypersensitivity to dostarlimab or any of its excipients * Allergy to any component of Chinese hamster ovary cells * History of severe active life-threatening autoimmune disease * History of uncontrolled or symptomatic cardiac disease. * Interstitial lung disease * Uncontrolled central nervous system metastases or carcinomatous meningitis * Patient has documented presence of HBsAg \[or HBcAb\] at screening or within 3 months prior to first dose of study intervention * Patient has a positive HCV antibody test result at screening or within 3 months prior to first dose of study intervention. NOTE: Participants with a positive HCV antibody test result due to prior resolved disease can be enrolled, only if a confirmatory negative HCV RNA test is obtained * Patient has a positive HCV RNA test result at Screening or within 3 months prior to first dose of study intervention. NOTE: The HCV RNA test is optional and participants with negative HCV antibody test are not required to undergo HCV RNA testing as well * Known HIV infection * Vaccinations (live vaccine) within 14 days prior to start of treatment * Immunosuppression, including subjects with conditions requiring systemic corticosteroid treatment (\>10 mg/day prednisone equivalent) * Active autoimmune disease requiring systemic treatment (vitiligo excluded) in the past 2 years or recent receipt within the previous 7 days of immunosuppressive therapy * History of organ transplantation * Pregnant or breastfeeding women * Patient has experienced any of the following with prior immunotherapy: any immune-related AE (irAE) of Grade 3 or higher, immune-related severe neurologic events of any grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain-Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade (Stevens-Johnson Syndrome, toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms \[DRESS\] syndrome), or myocarditis of any grade. Non-clinically significant laboratory abnormalities are not exclusionary * Any progressive disease that has not been balanced over the last 6 months: hepatic insufficiency, renal insufficiency, respiratory insufficiency, etc * Other cancer treated within the last 5 years except in situ cervical carcinoma or basocellular/ spinocellular carcinoma or a cancer of the lynch syndrome spectrum considered cured at the time of inclusion * Major surgery within 4 weeks before inclusion * Persons deprived of liberty or under guardianship or incapable of giving consent * Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol or follow-up schedule
Where this trial is running
Dijon
- CHU Dijon Bourgogne — Dijon, France (Recruiting)
Study contacts
- Study coordinator: Antoine KAROUI
- Email: mehdi.karoui@aphp.fr
- Phone: 0380293750
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.