Status and phase
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Study type
Funder types
Identifiers
About
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 :
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.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion criteria
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:
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
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
Non-inclusion criteria
Endocrine or acinar pancreatic carcinoma
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.
Major surgical procedure, 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
Known cerebral metastases, central nervous system (CNS), or epidural tumor
Prior anticancer treatment for adenocarcinoma of the pancreas including prior adjuvant or neoadjuvant treatment
Known dose tivity reaction to any of the components of study treatments.
Pregnancy (absence to be confirmed by β-hCG test) or breast-feeding period
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). Inclusion of patients with hypokalemia, hypomagnesemia and hypocalcemia (defined as results less than normal in Baseline testing) is not allowed.
Previous malignancy in the last 5 years except curative treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix
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.
Any significant disease which, in the investigator's opinion, would exclude the patient from the study.
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
Has undergone prior allogeneic hematopoietic stem cell transplantation
Has had an allogeneic tissue/solid organ transplant
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent)
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.
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.
History of or serology positive for HIV
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.
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.
Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
Has an active infection requiring systemic therapy
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.
In accordance with the updated SmPC of the products used in this trial, patient cannot be included in the following conditions:
Being deprived of liberty or under guardianship
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 6 months after the last dose of study treatment are not eligible for the study.
Primary purpose
Allocation
Interventional model
Masking
35 participants in 1 patient group
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Central trial contact
Asmahane BENMAZIANE TEILLET, Dr; Brigitte Bonneaudeau
Data sourced from clinicaltrials.gov
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