DOVIPA, a Study Evaluating Efficacy and Safety of DOstarlimab and VItamin D3 With mFOLFIRINOX in PAncreatic Cancer

NCT06757244 | Recruiting Phase 2 DMC

• 2 other identifiers: 2023_01112023-510004-49-00
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 5

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.

Conditions

Pancreas Neoplasms

Keywords

Pancreatic adenocarcinoma; metastatic PAncreatic Cancer; dostarlimab; vitamin D3; mFolfirinox; LV5FU

Outcome Measures

Primary Outcomes (1)

• 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)

  24 months

Secondary Outcomes (13)

• 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"

• 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"

• 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"

• 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"

• Median Progression Free Survival (mPFS) in months

  24 months

Study Arms (1)

Combination of mFOLFIRINOX plus dostarlimab and oral vitamin D3

EXPERIMENTAL

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.

Drug: Dostarlimab; Drug: Vitamin D3 (Cholecalciferol); Drug: mFOLFIRINOX Treatment Regimen; Drug: LV5FU2

Interventions

Dostarlimab DRUG

Intra-venous (i.v) dostarlimab: day1 - d21: 500mg IV q3Weeks (cycle 1 to cycle 4) then 1000 mg IV q6Weeks (from cycle 5 onwards)

Combination of mFOLFIRINOX plus dostarlimab and oral vitamin D3

Vitamin D3 (Cholecalciferol) DRUG

Oral vitamin D3 8000 IU/d for 14 days, then 4000IU/d

Combination of mFOLFIRINOX plus dostarlimab and oral vitamin D3

mFOLFIRINOX Treatment Regimen DRUG

mFOLFIRINOX 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.

Combination of mFOLFIRINOX plus dostarlimab and oral vitamin D3

LV5FU2 DRUG

folinic 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

Combination of mFOLFIRINOX plus dostarlimab and oral vitamin D3

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• Hopital Foch: lead
• GlaxoSmithKline: collaborator

Study Sites (5)

Marseille CRLCC

Marseille, France

NOT YET RECRUITING

CHU Hôtel Dieu

Nantes, France

NOT YET RECRUITING

Hôpital Européen Georges Pompidou

Paris, France

NOT YET RECRUITING

Hôpital Saint Antoine

Paris, France

NOT YET RECRUITING

Hôpital Foch

Suresnes, 92150, France

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

dostarlimab; Cholecalciferol

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Jaafar BENNOUNA, Pr

  Hôpital Foch

  STUDY DIRECTOR

Central Study Contacts

Asmahane BENMAZIANE TEILLET, Dr

CONTACT

0033146253619; a.benmaziane@hopital-foch.com

Tassadit Ben Belkacem

CONTACT

drci-promotion@hopital-foch.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Methodology: prospective, multicentric, non-randomised, open-label, safety-run in, phase 2 study.

Study Record Dates

• First Submitted: November 27, 2024
• First Posted: January 3, 2025
• Study Start: February 18, 2025
• Primary Completion (Estimated): February 18, 2028
• Study Completion (Estimated): February 18, 2028
• Last Updated: March 18, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)