DOVIPA, a Study Evaluating Efficacy and Safety of DOstarlimab and VItamin D3 with MFOLFIRINOX in PAncreatic Cancer
- Conditions
- Pancreas Neoplasms
- Interventions
- Registration Number
- NCT06757244
- Lead Sponsor
- Hopital Foch
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 35
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Combination of mFOLFIRINOX plus dostarlimab and oral vitamin D3 Dostarlimab Patients will be included and treated according to the following treatment regimen: * Intra-venous (i.v) dostarlimab: day1 - d21: 500mg IV q3Weeks (cycle 1 to cycle 4) then 1000 mg IV q6Weeks (from cycle 5 onwards) * Oral vitamin D3 8000 IU/d for 14 days, then 4000IU/d * mFOLFIRINOX d1, d15, d29 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 (cycle 1 to cycle 4). From cycle 5, the mFolfirinox will be substituted by LV5FU D1, D15 and D29. Combination of mFOLFIRINOX plus dostarlimab and oral vitamin D3 Vitamin D3 (Cholecalciferol) Patients will be included and treated according to the following treatment regimen: * Intra-venous (i.v) dostarlimab: day1 - d21: 500mg IV q3Weeks (cycle 1 to cycle 4) then 1000 mg IV q6Weeks (from cycle 5 onwards) * Oral vitamin D3 8000 IU/d for 14 days, then 4000IU/d * mFOLFIRINOX d1, d15, d29 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 (cycle 1 to cycle 4). From cycle 5, the mFolfirinox will be substituted by LV5FU D1, D15 and D29. Combination of mFOLFIRINOX plus dostarlimab and oral vitamin D3 mFOLFIRINOX Treatment Regimen Patients will be included and treated according to the following treatment regimen: * Intra-venous (i.v) dostarlimab: day1 - d21: 500mg IV q3Weeks (cycle 1 to cycle 4) then 1000 mg IV q6Weeks (from cycle 5 onwards) * Oral vitamin D3 8000 IU/d for 14 days, then 4000IU/d * mFOLFIRINOX d1, d15, d29 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 (cycle 1 to cycle 4). From cycle 5, the mFolfirinox will be substituted by LV5FU D1, D15 and D29. Combination of mFOLFIRINOX plus dostarlimab and oral vitamin D3 LV5FU2 Patients will be included and treated according to the following treatment regimen: * Intra-venous (i.v) dostarlimab: day1 - d21: 500mg IV q3Weeks (cycle 1 to cycle 4) then 1000 mg IV q6Weeks (from cycle 5 onwards) * Oral vitamin D3 8000 IU/d for 14 days, then 4000IU/d * mFOLFIRINOX d1, d15, d29 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 (cycle 1 to cycle 4). From cycle 5, the mFolfirinox will be substituted by LV5FU D1, D15 and D29.
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) according to Response Evaluation Criteria version 1.1 (RECIST 1.1) in patients with pancreatic adenocarcinoma and measurable disease 24 months 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)
- Secondary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0. From the initiation of study treatment until 90 days after the last dose or 30 days following cessation of study intervention if the participant initiates new anticancer therapy, whichever is earlier, assessed up to 24 months" 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. From the initiation of study treatment until 90 days after the last dose or 30 days following cessation of study intervention if the participant initiates new anticancer therapy, whichever is earlier, assessed up to 24 months" 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 From the initiation of study treatment until 90 days after the last dose or 30 days following cessation of study intervention if the participant initiates new anticancer therapy, whichever is earlier, assessed up to 24 months" 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 From the initiation of study treatment until 90 days after the last dose or 30 days following cessation of study intervention if the participant initiates new anticancer therapy, whichever is earlier, assessed up to 24 months" Number of participants with TEAEs leading to death will be assessed.
Median Progression Free Survival (mPFS) in months 24 months The median PFS will be assessed as the time after which half of the patients are progression-free and alive.
Median Overall Survival (mOS) in months 24 months The median OS will be assessed as the time after which half of the patients are alive.
Median Duration of Response (mDOR) in months 24 months the time from onset of first response (PR or CR as defined above) to progression or death due to any reason, whichever occurs first
Number of Participants With Immune Related Adverse Events (irAEs) From the initiation of study treatment until 90 days after the last dose or 30 days following cessation of study intervention if the participant initiates new anticancer therapy, whichever is earlier, assessed up to 24 months" The irAEs are events which may be severe or fatal according to CTCAE v5.0 and can occur in participants treated with monoclonal antibodies directed against immune checkpoints, including dostarlimab While irAEs (eg, diarrhea/colitis, pneumonitis, nephritis, hypophysitis, adrenalitis, thyroiditis, severe skin reactions, uveitis, myocarditis, and hepatotoxicity) usually occur during treatment, symptoms can also manifest after discontinuation of treatment.
Clinical benefit rate according to RECIST 1.1 (CBR) 24 months the proportion of patients with the Best Overall Response equal to Complete Response, Partial Response or Stable Disease, among all eligible patients.
Number of Participants With Adverse Events Leading to Discontinuation From the initiation of study treatment until 90 days after the last dose or 30 days following cessation of study intervention if the participant initiates new anticancer therapy, whichever is earlier, assessed up to 24 months" An AE is any event that was not present prior to the initiation of study treatment or any eventalready present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with adverse events leading to discontinuation will be assessed.
Incidence of patient premature discontinuations (due to SAE or non-adherence to protocol) From the initiation of study treatment until premature discontinuation due to serious adverse event or non adherence to protocol whichever is earlier, assessed up to 24 months" Incidence of serious adverse events or non adherence to protocol leading to discontinuation will be assessed.
Incidence of dose modifications From the initiation of study treatment until the last dose administration, assessed up to 24 months" Incidence of dose modifications due to the appearance of AEs (measured in dose modification compared with the protocol planned dose of treatments)
Incidence of delays or interruptions in the administration of treatment due to the appearance of AEs From the initiation of study treatment until the last dose administration, assessed up to 24 months" Incidence of delays or interruptions in the administration of treatment due to the appearance of AEs (measured in days or weeks since the initial scheduled date of treatment)
Trial Locations
- Locations (5)
Marseille CRLCC
🇫🇷Marseille, France
CHU Hôtel Dieu
🇫🇷Nantes, France
Hôpital Européen Georges Pompidou
🇫🇷Paris, France
Hôpital Saint Antoine
🇫🇷Paris, France
Hôpital Foch
🇫🇷Suresnes, France