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Dostarlimab for Locally Advanced or Metastatic Cancer (Non-colorectal/Non-endometrial) With Tumor dMMR/MSI

RecruitingPhase 2Ages 18 Years - anyAllUNICANCER
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In plain words

What the trial is, and whether it could suit you

The goal of this open-label randomized, multicenter, comparative phase II trial is to evaluate the efficacy of the immunotherapy, dostarlimab, as first-line treatment for deficient mismatch repair (dMMR)/microsatellite instability (MSI) non-resectable metastatic or locally advanced non-colorectal and non-endometrial cancers compared to the standard of care chemotherapy. Adult patients (aged ≥18 years) with histologically confirmed dMMR/MSI duodenum and small bowel adenocarcinoma, gastric and oeso-gastric junction (OGJ) adenocarcinoma with combined positive score (CPS)\<5, pancreatic adenocarcinoma, ampulla of vater adenocarcinoma, adrenocortical carcinoma, carcinoma of unknown primary site, neuroendocrine carcinoma (Grade3) all primary, and soft tissue sarcoma (except Gastro-Intestinal Stromal Tumor) will be included in this study. They will be randomized and treated with either dostarl

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📋 Eligibility rules (as published)
Inclusion Criteria: 1. Patient must have signed a written informed consent form prior any trial specific procedures. - 2. 18 years or older patients. 3. Documented locally advanced or metastatic disease with no previous systemic anti-cancer treatment in these settings and not suitable for complete surgical resection. 4. Histologically proven, dMMR/MSI-H solid tumors that are not colorectal or endometrial cancers and including one of the following: duodenum and small bowel adenocarcinoma, gastric and oeso-gastric junction adenocarcinoma with CPS\<5, pancreatic adenocarcinoma, ampulla of Vater adenocarcinoma, adrenocortical carcinoma, carcinoma of unknown primary site, neuroendocrine carcinoma (Grade 3) all primary, and soft tissue sarcoma except Gastro-Intestinal Stromal Tumor (GIST). 5. If patient received adjuvant therapy for non-metastatic disease, this therapy should be completed more than 6 months before the diagnosis of metastatic or recurrent disease. 6. Availability of minimum 1 block of tumor tissue or 20 slides (archival (\<2 years) or fresh biopsy specimen of primary and or metastasis) for centralized confirmation of MMR/MSI status by IHC or NGS/PCR, and for Translational Research. 7. Patients with dMMR/MSI tumor analyzed by IHC, PCR (for Gastric and OGJ adenocarcinoma, and duodenum and small bowel adenocarcinoma only), and/or NGS at the recruiting center should be confirmed by central review within 24h (every anonymized patient analysis reporting will be provided for central review). Patients should not be included in the study until the dMMR/MSI status is confirmed by the review committee. NB: In case of ambiguous result of IHC (lack of positive internal control, heterogeneous loss of MMR protein expression, ambiguous loss of only one protein including HMSH6 and PMS2), the MSI-H status will be assessed by PCR or NGS for gastric and OGJ adenocarcinoma, and duodenum and small bowel adenocarcinoma, and by NGS for other primary. Based on IHC and PCR or NGS results (NGS will be centrally performed in this case ), the sponsor will decide if inclusion is possible; 8. Presence of at least one measurable lesion within 28 days before the start of treatment according to RECIST v1.1. 9. Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1. 10. Haematological status: absolute neutrophil count (ANC) ≥1.5 x 10⁹/L; platelets ≥100 x 10⁹/L; haemoglobin ≥9 g/dL. 11. Adequate renal function: serum creatinine level \<120 µM, or clearance \>50 ml/min (Modification of the Diet in Renal Disease \[MDRD\] or Cockcroft and Gault). 12. Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x ULN, unless liver metastases are present, in which case they must be ≤ 5× ULN. 13. For patients not taking warfarin: International normalised ratio (INR) \<1.5 or prothrombin time (PT) \<1.5 x ULN and either partial thromboplastin time (PTT) or activated PTT (aPTT) \<1.5 x ULN. Participants taking warfarin may be included on a stable dose with a therapeutic INR \<3.5. 14. Women of childbearing potential must have a negative serum pregnancy test performed within 72 hours before the date of randomization. 15. Men, and women of childbearing potential must agree to use adequate contraception for the duration of trial participation and for 4 months after the last dose of dostarlimab (used in first line or at crossover) or for at least 6 months after the last administration of the chemotherapy agent(s) used in the control arm if no crossover with dostarlimab (according to the current version of the summary of product characteristics (SmPC) of each chemotherapy agent). Men must also agree to not donate sperm and women must agree to not donate oocytes during the specified period. 16. Registration in a National Health Care System. 17. Patient is willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study. Exclusion Criteria: 1. Colorectal and endometrial cancer and all primary tumor not listed in inclusion criterion #4. 2. Previous exposure to anti-PD-1 or PD-L1 or anti-CTL-4 antibodies or treatment with immunotherapy. 3. Previous exposure to any investigational drug within 4 weeks (6 weeks for monoclonal antibodies) before the first dose in the study. 4. Previous exposure to any systemic anti-cancer therapy or radiation therapy for the cancer for which the patient is being enrolled. 5. Active autoimmune disease: Active autoimmune disease requiring systemic treatment in the past 2 years (excluding replacement therapy) or any history of interstitial lung disease (patients with ancient auto-immune disease with stable endocrine oral substitution are eligible). 6. Uncontrolled central nervous system metastases or carcinomatous meningitis or other concurrent illness or ongoing or active infections. 7. Patients with HER2-positive gastric carcinoma. 8. Other serious and uncontrolled non-malignant disease or is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active infection requiring systemic therapy. Specific examples include, but are not limited to, active, non-infectious pneumonitis; uncontrolled ventricular arrhythmia; recent (within 90 days) myocardial infarction; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study. 9. Prior allogeneic bone marrow transplantation or prior solid organ transplantation. 10. Has received treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to the first dose of adjuvant
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What it tests

  • Dostarlimab
  • Chemotherapy
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Where

22 sites
Institut de Cancérologie de l'Ouest
Angers, France
Institut du Cancer Avignon-Provence
Avignon, France
CHU Jean Minjoz
Besançon, France
CHU Morvan
Brest, France
Centre François Baclesse
Caen, France
Centre Jean Perrin
Clermont-Ferrand, France
CHU - Henri Mondor
Créteil, France
Centre Georges François Leclerc
Dijon, France

…and 14 more on ClinicalTrials.gov.

🤝 Taking part is your choice, and you can leave at any time. Only the trial team can confirm you are eligible — always decide together with your own doctor.
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