Rectal Adenocarcinoma with Mismatch-repair Deficient (dMMR)/ Microsatellite Instability-high (MSI-H)Phase 3PREDIR-NEORECNCT06762405
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
A Phase 3 study testing radiotherapy, Dostarlimab and Biological study on circulating tumor DNA (optional for the patient) in people with Rectal Adenocarcinoma with Mismatch-repair Deficient (dMMR)/ Microsatellite Instability-high (MSI-H), run by Centre Hospitalier Universitaire Dijon at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Adenocarcinoma with Mismatch-repair Deficient (dMMR)/ Microsatellite Instability-high (MSI-H)
- What is being tested?
- radiotherapy, Dostarlimab and Biological study on circulating tumor DNA (optional for the patient)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteFrance
- Study dates
- 6 Feb 2025to Sep 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
CHU Dijon Bourgogne
Dijon, 21000
Antoine DROUILLARD, 0380293750 ext. +33, antoine.drouillard@chu-dijon.fr
About this study
Official title: 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
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)
- Being tested
- radiotherapy, Dostarlimab, Biological study on circulating tumor DNA (optional for the patient)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
radiotherapyRadiation
short course of radiotherapy (5 grays × 5 days)
DostarlimabDrug
dostarlimab 500 mg intravenous infusion every 3 weeks for 6 months (nine cycles)
Biological study on circulating tumor DNA (optional for the patient)Biological
- 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
| Study group | Role | What they receive |
|---|---|---|
| Radiotherapy followed by Dostarlimab arm | Experimental | Not described Receives: Radiation: radiotherapy; Drug: Dostarlimab; Biological: Biological study on circulating tumor DNA (optional for the patient) |
| Dostarlimab alone arm | Active comparator | Not described Receives: Drug: Dostarlimab; Biological: Biological study on circulating tumor DNA (optional for the patient) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment strategy failure (TSF) rate.
TSF is defined as the rate of patients without a clinical complete response (cCR) regarding all the clinical exams (Digital Rectal Exam, MRI and Endoscopy) and those with a cCR but with local or metastatic recurrence or local regrowth within 2 years.
Measured: at 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2025
- Study start6 Feb 2025
- Primary completionSep 2030 (estimated)
- Study completionSep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal Adenocarcinoma with Mismatch-repair Deficient (dMMR)/ Microsatellite Instability-high (MSI-H)Studies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire DijonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire Dijon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06762405
- Sponsor's protocol ID
- DROUILLARD PHRCK 2023-1
- Acronym
- PREDIR-NEOREC
- Status last verified
- Feb 2025
- First submitted
- 31 Dec 2024
- Last updated
- 18 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06762405
- Acronym / sponsor ID
- PREDIR-NEOREC / DROUILLARD PHRCK 2023-1
- Conditions
- Rectal Adenocarcinoma with Mismatch-repair Deficient (dMMR)/ Microsatellite Instability-high (MSI-H)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- Centre Hospitalier Universitaire DijonUniversity, hospital or other
- Study start
- 6 Feb 2025 (actual)
- Primary completion
- Sep 2030 (estimated)
- Study completion
- Sep 2030 (estimated)
- First posted
- 7 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Radiotherapy followed by Dostarlimab arm | Experimental | Radiation: radiotherapy, Drug: Dostarlimab, Biological: Biological study on circulating tumor DNA (optional for the patient) |
| Dostarlimab alone arm | Active comparator | Drug: Dostarlimab, Biological: Biological study on circulating tumor DNA (optional for the patient) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| radiotherapyshort course of radiotherapy (5 grays × 5 days) | Radiation | Radiotherapy followed by Dostarlimab arm |
| Dostarlimabdostarlimab 500 mg intravenous infusion every 3 weeks for 6 months (nine cycles) | Drug | Dostarlimab alone arm, Radiotherapy followed by Dostarlimab arm |
| 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 | Biological | Dostarlimab alone arm, Radiotherapy followed by Dostarlimab arm |
Primary outcome
Treatment strategy failure (TSF) rate.
Time frame: at 24 months
TSF is defined as the rate of patients without a clinical complete response (cCR) regarding all the clinical exams (Digital Rectal Exam, MRI and Endoscopy) and those with a cCR but with local or metastatic recurrence or local regrowth within 2 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing radiotherapy, Dostarlimab and Biological study on circulating tumor DNA (optional for the patient) in people with Rectal Adenocarcinoma with Mismatch-repair Deficient (dMMR)/ Microsatellite Instability-high (MSI-H), run by Centre Hospitalier Universitaire Dijon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Antoine KAROUI (0380293750 ext. +33, mehdi.karoui@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment strategy failure (TSF) rate. (time frame: at 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2025.