DOVIPA, a Phase II Study Evaluating Efficacy and Safety of DOstarlimab and Oral VItamin D3 With Folinic Acid, 5FU, Irinotecan Plus Oxalipaltin (mFOLFIRINOX) in Non Pretreated Metastatic PAncreatic Cancer
The goal of this clinical trial is to estimate the antitumor response of mFOLFIRINOX + Dostarlimab + oral HD vitamin D3 in patients with non-pretreated histologically confirmed metastatic Stage IV adenocarcinoma of the pancreas. The patients must have an Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS) 0 or 1 and adequate organ functions. The main objective of the study will be assessed by estimating Objective response rate (ORR) according to Response Evaluation Criteria version 1.1 (RECIST 1.1) in patients with pancreatic adenocarcinoma and measurable disease. The Secondary objectives are : * To assess the safety and tolerability of mFOLFIRINOX + Dostarlimab + HD Vitamin D according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 by evaluating the Median Progression Free Survival (mPFS) in months, the Median Overall Survival (mOS) in months, the Median Duration of Response (mDOR) in months and Clinical benefit rate according to RECIST 1.1 (CBR) * To further evaluate the antitumor efficacy of mFOLFIRINOX + Dostarlimab + oral HD Vitamin D by evaluating the type, frequency, and severity of treatment-emergent adverse events (TEAEs); adverse events of special interest (AESIs); safety laboratory findings There are also exploratory objectives to better understand the pancreatic adenocarcinoma. Participants will be cared for in the digestive oncology department. A selection review will be carried out to check compliance with the study eligibility criteria. Patients included in the study will be treated with 4 cycles of induction therapy. Each cycle lasts 6weeks and includes chemotherapy such as mFolfirinox D1,D15 and D29, combined with dostarlimab 500 mg every 3 weeks and daily oral vitamin D3. At the end of the induction treatment period, maintenance treatment will be instituted with LV5FU chemotherapy combined with dostarlimab 1000 mg every 6 weeks and daily oral vitamine D3. Treatment will be maintained until progression or unacceptable toxicity. Throughout this period, patients will be monitored for their safety. Imaging examinations will also be carried out to monitor the progression of tumour disease.
• Histologically confirmed metastatic Stage IV adenocarcinoma of the pancreas
• No prior treatment for stage IV pancreatic adenocarcinoma (prior adjuvant or neoadjuvant treatment is not allowed)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
• Male and female patients 18 - 75 years
• Measurable disease determined using guidelines of Response Evaluation Criteria In Solid Tumors (RECIST version 1.1)
• Accessible tumor tissue available for fresh biopsy
• Expected survival \>3 months
• Men and women of child-bearing potential must agree to use adequate contraception.
• A female participant is eligible to participate if she is not pregnant or breastfeeding and at least one of the following conditions applies:
⁃ Is not a woman of childbearing potential (WOCBP), or
⁃ Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), from the screening visit to at least 6 months after the last dose of study treatment, and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of dostarlimab, and A WOCBP must have a negative highly sensitive pregnancy test (urine or serum, as required by local regulations) within 72 hours before the first dose of study treatment.
• Fertile men who are sexually active with a WOCBP must use a male condom plus spermicide during the trial and for 6 months after the last dose of study treatment administration. Male patients should also refrain from sperm donation throughout this period.
• Laboratory values ≤1 week prior to randomization must be Adequate hematologic values
‣ Platelet count ≥100,000 cells/mm3
⁃ Absolute neutrophil count \[ANC\] ≥1,500 cells/mm3
⁃ Hemoglobin ≥9 g/dL or ≥90 g/L) Adequate hepatic function
⁃ Aspartate aminotransferase \[AST/SGOT\] ≤2.5x Upper Normal Limit \[UNL\] (≤5x UNL if liver metastases present)
⁃ Alanine aminotransferase \[ALT/SGPT\] ≤ 2.5x Upper Normal Limit (≤5x UNL if liver metastases present)
⁃ Bilirubin ≤1.5x UNL
⁃ Serum albumin \> 3.0 g/dL Adequate renal function serum creatinine clearance CLcr ≥ 50 mL/min) (Cocroft-Gault Formula should be used for CrCl calculation) For participants not taking warfarin: INR \<1.5 or PT \<1.5 x ULN and either PTT or aPTT \<1.5 x ULN. Participants taking warfarin may be included on a stable dose with a therapeutic INR \<3.5 Uracilemia \< 16 ng/ml
⁃ Patients with history of hepatitis C (HCV) infection are eligible if HCV viral load is undetectable at screening. HCV screening tests are not required unless there is a known history of HCV infection.
⁃ No evidence of active infection and no serious infection within the past 30 days.
⁃ Patient able to understand and willing to sign and date the written voluntary informed consent form at screening visit prior to any protocol-specific procedures
⁃ Patient affiliated to a social security regimen