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
None
Single group
Dostarlimab
DrugIntra-venous (i.v) dostarlimab: day1 - d21: 500mg IV q3Weeks (cycle 1 to cycle 4) then 1000 mg IV q6Weeks (from cycle 5 onwards)
Vitamin D3 (Cholecalciferol)
DrugOral vitamin D3 8000 IU/d for 14 days, then 4000IU/d
mFOLFIRINOX Treatment Regimen
DrugmFOLFIRINOX d1, d15, d29 cycle 1 to cycle 4 is administered as follow: oxaliplatin 85 mg/m2 on day1, IV infusion over 2 h, immediately followed by folinic acid 400 mg/m2 or calcium levofolinate 200 mg/m2 given as a 2-h IV infusion, with the addition of irinotecan 180 mg/m2 as per dose-level given as a 90-min intravenous infusion through a Y-connector immediately followed by 5- fluorouracil 2400 mg/m2 over 46 h continuous infusion.
LV5FU2
Drugfolinic acid 400 mg/m2 Or calcium levofolinate 200 mg/m2 2-h IV infusion 5- fluoro-uracil 2400 mg/m2 Over 46 h continuous infusion. From cycle 5 onwards, D1=D43
Objective response rate (ORR) according to Response Evaluation Criteria version 1.1 (RECIST 1.1) in patients with pancreatic adenocarcinoma and measurable disease
The proportion of patients with an objective response at the completion of their follow-up (truncated at 24 months), among all eligible patients. An objective response will be defined as the best overall response of complete response (CR) or partial response (PR) assessed by investigators using validated criteria (i.e. RECIST 1.1)
Incidence of treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0.
The number and percentage of participants experiencing at least one treatment-emergent adverse event (TEAE) will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. TEAEs are defined as adverse events occurring after the initiation of study treatment and before 90 days after the last dose or 30 days following cessation of study intervention if the participant initiates new anticancer therapy, whichever is earlier, must be reported by the investigator, or an already present event that worsens in intensity or frequency following the treatment. TEAEs will be categorized by type (serious or non-serious; expected or unexpected) and severity (CTCAE grades 1 to 5) as per investigator assessment
Incidence of participants with adverse events of special interest (AESIs) as assessed by CTCAE v5.0.
The number and percentage of participants experiencing at least one adverse events of special interest (AESIs) will be summarized. AESIs are pre-defined events requiring detailed monitoring and rapid communication by the investigator due to their potential association with the investigational product. The severity of AESIs will be graded using CTCAE v5.0 (CTCAE grades 1 to 5).
Number of Participants With Clinically Significant Changes in Hematology, Clinical Chemistry, Thyroid Function and Urinalysis Lab Parameters
Blood and urine samples will be collected to evaluate hematology, clinical chemistry, thyroid function and urinalysis lab parameters . Changes from baseline to post-baseline visits will be computed. Final values and changes from baseline in continuous variables will be described et each visit. Clinically significant laboratory abnormalities (as defined by CTCAE v5.0 criteria) will also be reported.
Number of Participants With AEs Leading to Death
Number of participants with TEAEs leading to death will be assessed.
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Hopital Foch
Lead sponsor
GlaxoSmithKline
Collaborator
