Informations générales (source: ClinicalTrials.gov)
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 (DOVIPA)
Interventional
Phase 2
Hopital Foch (Voir sur ClinicalTrials)
février 2025
février 2028
05 avril 2025
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.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Europeen Georges Pompidou | Julien TAIEB, Dr | Contact (sur clinicalTrials) | |||
| AP-HP - Hôpital Saint Antoine | Isabelle Trouilloud, Dr | Contact (sur clinicalTrials) | |||
| HOPITAL FOCH | Asmahane Benmaziane, Dr | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CHU Hôtel Dieu - Nantes - France | Fanny FOUBERT, Dr | Contact (sur clinicalTrials) | |||
| Marseille CRLCC - Marseille - France | Jean Emmanuel Mitry, Dr | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion criteria
1. Histologically confirmed metastatic Stage IV adenocarcinoma of the pancreas
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 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.
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
Non-inclusion criteria
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. 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
4. Known cerebral metastases, central nervous system (CNS), or epidural tumor
5. Prior anticancer treatment for adenocarcinoma of the pancreas including prior
adjuvant or neoadjuvant treatment
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. 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.
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. 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. Any significant disease which, in the investigator's opinion, would exclude the
patient from the study.
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. Has undergone prior allogeneic hematopoietic stem cell transplantation
14. Has had an allogeneic tissue/solid organ transplant
15. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent)
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. 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. History of or serology positive for HIV
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. 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. Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease
22. Has an active infection requiring systemic therapy
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.
In accordance with the updated SmPC of the products used in this trial, patient
cannot be included in the following conditions:
- patient has a peripheral sensitive neuropathy with functional impairment prior
to first course (contra-indication use with Oxaliplatin)
- concomitant use with St John's Wort - Chronic inflammatory bowel disease and/or
bowel obstruction (contra-indication with Irinotecan)
- patient which has been treated with brivudine, sorivudine or their chemically
related analogues, which are potent inhibitors of the enzyme dihydropyrimidine
dehydrogenase (DPD), which degrades fluorouracil. Fluorouracil must not be
taken within 4 weeks of treatment with brivudine, sorivudine or their
chemically related analogues (contra-indication with fluorouracil)
- patient has diseases/conditions associated hypercalcaemia and / or
hypercalciuria. - Calcium nephrolithiasis, nephrocalcinosis, D-
hypervitaminosis
24. Being deprived of liberty or under guardianship
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 6 months after the last dose of study treatment are not
eligible for the study.
1. Histologically confirmed metastatic Stage IV adenocarcinoma of the pancreas
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 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.
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
Non-inclusion criteria
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. 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
4. Known cerebral metastases, central nervous system (CNS), or epidural tumor
5. Prior anticancer treatment for adenocarcinoma of the pancreas including prior
adjuvant or neoadjuvant treatment
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. 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.
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. 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. Any significant disease which, in the investigator's opinion, would exclude the
patient from the study.
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. Has undergone prior allogeneic hematopoietic stem cell transplantation
14. Has had an allogeneic tissue/solid organ transplant
15. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent)
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. 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. History of or serology positive for HIV
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. 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. Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease
22. Has an active infection requiring systemic therapy
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.
In accordance with the updated SmPC of the products used in this trial, patient
cannot be included in the following conditions:
- patient has a peripheral sensitive neuropathy with functional impairment prior
to first course (contra-indication use with Oxaliplatin)
- concomitant use with St John's Wort - Chronic inflammatory bowel disease and/or
bowel obstruction (contra-indication with Irinotecan)
- patient which has been treated with brivudine, sorivudine or their chemically
related analogues, which are potent inhibitors of the enzyme dihydropyrimidine
dehydrogenase (DPD), which degrades fluorouracil. Fluorouracil must not be
taken within 4 weeks of treatment with brivudine, sorivudine or their
chemically related analogues (contra-indication with fluorouracil)
- patient has diseases/conditions associated hypercalcaemia and / or
hypercalciuria. - Calcium nephrolithiasis, nephrocalcinosis, D-
hypervitaminosis
24. Being deprived of liberty or under guardianship
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 6 months after the last dose of study treatment are not
eligible for the study.