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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospital Foch

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Feb 2025 → ongoing

Decision date (initial)

2024-08-01

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To estimate the antitumor response of mFOLFIRINOX + Dostarlimab + oral HD vitamin D3 in patients in with non pretreated metastatic pancreatic Cancer.

Secondary objectives 2

1. To assess the safety and tolerability of mFOLFIRINOX + Dostarlimab + HD Vitamin D3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
2. To evaluate the antitumor efficacy of mFOLFIRINOX + Dostarlimab + HD Vitamin D3

Conditions and MedDRA coding

non pretreated metastatic PAncreatic Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Histologically confirmed metastatic Stage IV adenocarcinoma of the pancreas
2. 2. No prior treatment for stage IV pancreatic adenocarcinoma (prior adjuvant or neoadjuvant treatment is not allowed)
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 – 1
4. Male and female patients 18 – 75 years
5. Measurable disease determined using guidelines of Response Evaluation Criteria In Solid Tumors (RECIST version 1.1)
6. Accessible tumor tissue available for fresh biopsy
7. Expected survival >3 months
8. 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 4 months after the last dose of dostarlimab, 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 120 days after the last dostarlimab administration. Male patients should also refrain from sperm donation throughout this period.
9. 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
10. 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.
11. No evidence of active infection and no serious infection within the past 30 days.
12. 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
13. Patient affiliated to a social security regimen

Exclusion criteria 25

1. Endocrine or acinar pancreatic carcinoma
2. Participant has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice. Note: Stable non-cirrhotic chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria.
3. 3. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to study treatment start. Incompletely healed wounds or anticipation of the need for major surgical procedure during the course of the study
4. Known cerebral metastases, central nervous system (CNS), or epidural tumor
5. Prior anticancer treatment for adenocarcinoma of the pancreas
6. Known dose tivity reaction to any of the components of study treatments.
7. Pregnancy (absence to be confirmed by β-hCG test) or breast-feeding period
8. 8. Clinically relevant coronary artery disease or history of myocardial infarction in the last 6 months, or high risk of uncontrolled arrhythmia (for men: QTc ≥450 msec, for women: QTc ≥470 msec)
9. 9. Previous malignancy in the last 5 years except curative treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix
10. 10. History or current evidence on physical examination of central nervous system disease or peripheral neuropathy ≥ grade 1 Common Toxicity Criteria for Adverse Events (CTCAE) v5.0.
11. 11. Any significant disease which, in the investigator’s opinion, would exclude the patient from the study.
12. 12. Patient with a DPD deficiency or UGT1A1 homozygous 7/7; the test should be done for all patients before 5-FU administration, according to ANSM communication regarding recommendation about high risk of no testing DPD in patient before 5-FU administration
13. 13. Has undergone prior allogeneic hematopoietic stem cell transplantation
14. 14. Has had an allogeneic tissue/solid organ transplant
15. 15. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent)
16. 16. Participant has received systemic steroid therapy (>10 mg daily prednisone or equivalent) within 7 days before the first dose of the study treatment or is receiving any other form of immunosuppressive medication. Replacement therapy (adrenal or pituitary insufficiency) is not considered a form of systemic therapy. Use of inhaled corticosteroids, local steroid injection, or steroid eye drops is allowed.
17. 17. Participant has received a live vaccine within 30 days of planned start of study therapy. COVID-19 vaccines that do not contain live viruses are allowed. Note: mRNA and adenoviral-based COVID-19 vaccines are considered non-live.
18. 18. History of or serology positive for HIV
19. 19. Patients who have documented presence of HBsAg [or HBcAb] at Screening or within 3 months prior to first dose of study intervention are excluded. HBV screening tests are not required unless there is a known history of HBV infection.
20. 20. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
21. 21. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
22. 22. Has an active infection requiring systemic therapy
23. 23. Allergy: Participant cannot have history of severe allergic and/or anaphylactic reactions to chimeric, human or humanized antibodies or fusion proteins, sensitivity to any of the study treatments or components thereof, or a history of drug or other allergy that contraindicates their participation.
24. 24. Being deprived of liberty or under guardianship
25. 25. Potential participants who are pregnant, breastfeeding, or expecting to conceive children while receiving study treatment and/or unwilling to use highly effective contraception for up to 4 months after the last dose of study treatment are not eligible for the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of this study is the Objective Response Rate (ORR).

Secondary endpoints 2

1. 1. To assess the safety and tolerability of mFOLFIRINOX + dostarlimab + HD vitamin D3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
2. 2. To evaluate the antitumor efficacy of mFOLFIRINOX + dostarlimab + HD Vitamin D3.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospital Foch

Sponsor organisation

Hospital Foch

Address

40 Rue Worth

City

Suresnes

Postcode

92150

Country

France

Scientific contact point

Organisation

Hospital Foch

Contact name

Pr. Jaafar BENNOUNA

Public contact point

Organisation

Hospital Foch

Contact name

Pr. Jaafar BENNOUNA

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications