DOSTARLIMAB for Locally advanced rectal cancer (mismatch repair-deficient / microsatellite instability-high)

Inclusion criteria

• {"criterion_text":"- Age ≥18 years"}
• {"criterion_text":"- Middle and lower third rectal adenocarcinoma (diagnosed on the basis of standard clinical and MRI criteria)"}
• {"criterion_text":"- •\tParticipant receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- T2-T4 Nany and Tany N+ disease"}
• {"criterion_text":"- WHO performance status 0 or 1"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Negative pregnancy test done 72 hours prior to registration, for women of childbearing potential only. 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"}
• {"criterion_text":"- Ability of patient to understand, sign and date the informed consent form before any study specific screening procedures"}
• {"criterion_text":"- Patient affiliated to a social security scheme"}

Exclusion criteria

• {"criterion_text":"- Upper third rectal adenocarcinoma (above 10 cm from the anal verge or sus-peritoneal on standard clinical and MRI criteria)"}
• {"criterion_text":"- Patients who have already received immunotherapy, chemotherapy or radiotherapy for rectal cancer"}
• {"criterion_text":"- Any progressive disease that has not been balanced over the last 6 months: hepatic insufficiency, renal insufficiency, respiratory insufficiency, etc"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Persons deprived of liberty or under guardianship or incapable of giving consent"}
• {"criterion_text":"- Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol or followup schedule"}
• {"criterion_text":"- Participant has an active infection requiring systemic therapy within 1 week prior to the anticipated first dose of study treatment."}
• {"criterion_text":"- Contraindication to pelvic radiotherapy"}
• {"criterion_text":"- Hypersensitivity to dostarlimab or any of its excipients"}
• {"criterion_text":"- Allergy to any component of Chinese hamster ovary cells."}
• {"criterion_text":"- History of severe active life-threatening autoimmune disease"}
• {"criterion_text":"- Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected)."}
• {"criterion_text":"- Interstitial lung disease"}
• {"criterion_text":"- Uncontrolled central nervous system metastases or carcinomatous meningitis"}
• {"criterion_text":"- Reccurent rectal cancer"}
• {"criterion_text":"- •\tPatient 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"}
• {"criterion_text":"- Tumor is causing symptomatic bowel obstruction (diverting stoma (ileostomy or colostomy) is allowed in case of obstructive rectal cancer. Bowel obstruction should not be an exclusion criteria as the obstruction has been relieved by a diverting stoma. It should be reminded that a stent is not recommended but not excluded in mid and low rectal cancer)"}
• {"criterion_text":"- Known HIV infection"}
• {"criterion_text":"- Vaccinations (live vaccine) within 14 days prior to start of treatment"}
• {"criterion_text":"- Immunosuppression, including subjects with conditions requiring systemic corticosteroid treatment (>10 mg/day prednisone equivalent)"}
• {"criterion_text":"- Active autoimmune disease requiring systemic treatment within the past 2 years or documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents at non-physiologic doses"}
• {"criterion_text":"- History of organ transplantation"}
• {"criterion_text":"- Pregnant or breastfeeding women"}

Primary endpoints

• {"endpoint_text":"- The primary objective is to evaluate the treatment strategy failure (TSF) rate at 24 months from the date of randomization.","definition_or_measurement_approach":"Failure being defined as the absence of clinical complete response (cCR, Digital Rectal Examination, MRI and Endoscopy) and/or local or distant disease progression. Absence of clinical complete response is defined as failure in 1 or more of the measurement parameters such DRE, MRI, Endoscopy."}

Secondary endpoints

• {"endpoint_text":"- Adverse events (AEs) assessed according to NCI-CTCAE v5.0 will be presented by the number of patients with at least one AE by maximum grade and by causality to treatment (dostarlimab).","definition_or_measurement_approach":"AEs assessed per NCI-CTCAE v5.0; presented by number of patients with at least one AE, by maximum grade and by causality to dostarlimab."}
• {"endpoint_text":"- Disease Free Survival (DFS): DFS is defined by the time between the date of randomization and the date of disease recurrence including local, locoregional or metastatic relapse, second colorectal cancer, death whatever the cause of death. Patients alive without recurrence or second cancer will be censored at date of last news. The rate of alive patients without recurrence or second cancer will be done at 6, 12, 24 and 36 months.","definition_or_measurement_approach":"DFS defined as time from randomization to disease recurrence (local, locoregional, metastatic), second colorectal cancer, or death. Censoring at last follow-up for patients alive without recurrence. Rates calculated at 6, 12, 24, 36 months."}
• {"endpoint_text":"- Overall survival (OS): OS is defined by the time between the date of randomization and the date of death (regardless of the cause). Alive patients will be censored at date of last news. The rate of alive patients will be done at 6, 12, 24 and 36 months","definition_or_measurement_approach":"OS defined as time from randomization to death from any cause; censoring at last follow-up for alive patients. Rates at 6, 12, 24, 36 months."}
• {"endpoint_text":"- The rate of organ preservation at 2 years is defined at the rate of patients without resection of primary tumor (local excision, TME surgery, permanent colostomy/ileostomy) at 2 years. The rate of local excision, TME (total mesorectal excision) surgery or creation of a permanent colostomy/ileostomy at 2 years is defined as the rate of patients with surgery at 2 years.","definition_or_measurement_approach":"Organ preservation: proportion of patients without primary tumor resection (local excision, TME, permanent colostomy/ileostomy) at 2 years. Surgery rate defined as proportion with such surgery at 2 years."}
• {"endpoint_text":"- Quality of life: Quality of life will be assessed according to the questionnaire of EORTC QLQ-C30 and QLQ-CR29 scales (at baseline, 3, 6, 12 and 24 months). Scores will be described at inclusion by treatment arm. The time to final deterioration of the global health score will be calculated: it is defined as the time from the date of randomisation to the date of deterioration of more than 10 points compared to the inclusion score (without any improvement later) or death. Alive patients without d","definition_or_measurement_approach":"QoL assessed using EORTC QLQ-C30 and QLQ-CR29 at baseline, 3, 6, 12, 24 months. Time to final deterioration defined as time from randomization to a sustained >10-point deterioration in global health score or death; scores summarized by arm."}
• {"endpoint_text":"- Objective response rate (ORR): Objective Response rate is defined by patients with partial or complete response. The best tumor response will be evaluated throughout the treatment. The response is evaluated according to the various categories: complete, partial, stability, progression or non-evaluable response.","definition_or_measurement_approach":"ORR = proportion of patients with complete or partial response. Best tumor response evaluated during treatment and categorized as complete, partial, stable, progression, or non-evaluable."}

France

Earliest CTIS Part Ii Submission Date

19-07-2024

Latest Decision Or Authorization Date

13-02-2026

Processing Time Days

574

Number Of Participants

68

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Dijon

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"Fondation Franc.Cancerologie Digestive","duties_or_roles":"1|10|5|6|8","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"","full_name":"Fédération Francophone de Cancérologie Digestive","duties_or_roles":"Monetary support","organisation_type":""}