Trial Title:
Study Investigating the Association of NP137 With mFOLFIRINOX in Locally Advanced Pancreatic Ductal Adenocarcinoma
NCT ID:
NCT05546853
Condition:
Pancreatic Ductal Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Leucovorin
Oxaliplatin
Irinotecan
Calcium
Levoleucovorin
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Multicentric prospective single arm phase 1b trial.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
NP137
Description:
NP137 will be administrated at the first day of each cycle (CnD1) of 14 days as an IV
infusion at 9 or 14 mg/kg.
Arm group label:
Experimental
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
Oxaliplatin will be administreted at the first day of each cycle (CnD1) of 14 days as an
IV infusion at 85 mg/m²
Arm group label:
Experimental
Intervention type:
Drug
Intervention name:
Irinotecan
Description:
Irinotecan will be administreted at the first day of each cycle (CnD1) of 14 days as an
IV infusion at 150 mg/m²
Arm group label:
Experimental
Intervention type:
Drug
Intervention name:
Calcium levofolinate
Description:
Calcium levofolinate will be administreted at the first day of each cycle (CnD1) of 14
days as an IV infusion at 100 mg/m²
Arm group label:
Experimental
Intervention type:
Drug
Intervention name:
5 FU
Description:
5 FU will be administreted at the first day of each cycle (CnD1) of 14 days as an IV
infusion at 2400 mg/m2 as a continuous intravenous infusion over 46 hours.
Arm group label:
Experimental
Summary:
The study will assess the safety of the association of NP137 with the standard of care
mFOLFIRINOX in the treatment of locally advanced pancreatic ductal adenocarcinoma.The
study drug which is tested is the NP137 in association with mFOLFIRINOX to allow a better
tumor response as well as better survival outcomes with an acceptable safety.
Detailed description:
The study is a multicentric, prospective, single arm phase 1b trial. This study will
enroll 43 to 52 patients and consists of 2 parts: Safety Lead-in Phase and Expansion
Phase. Initially, 3 to 12 patients will be enrolled into a Safety Lead-in Phase based on
a 3 + 3 design, with the possibility of dose de-escalation, to confirm the recommended
dose of NP137.The Expansion Phase will start after completion of Safety Lead-in Phase at
the confirmed dose and will include 40 patients. Patients will be assigned to the
experimental arm (NP137 + mFOLFIRINOX).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age from 18 to 79 years
2. Able to understand and sign informed consent
3. Histologically or cytologically proven diagnosis of pancreatic ductal adenocarcinoma
4. Locally advanced pancreatic cancer considered unresectable according to NCCN
Guidelines® Version 2.2021
5. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors RECIST
1.1 criteria
6. Male, or non-pregnant and non-lactating female
7. Women patients of childbearing potential* must have a negative serum/urine pregnancy
test at screening and baseline, and be willing to use a highly effective**
contraception. The patient should be advised to continue the contraception for at
least 6 months following the completion of dosing. Women with cessation for > 24
months of previously occurring menses, or women of any age who have had a
hysterectomy, or have had both ovaries removed will be considered to be of
non-childbearing potential
8. Male patients of reproductive potential must be willing to use one acceptable method
of contraception, as judged by Investigator and Sponsor and/or to refrain from
donating sperm from the time of screening through at least 6 months following the
completion of dose administration
9. No prior systemic therapy, radiation therapy, or resection for pancreatic cancer
10. Life expectancy ≥ 12 weeks
11. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
12. Adequate liver function:
1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x
upper limit of normal (ULN),
2. Bilirubin ≤ 1.5 x ULN or in subjects with biliary stenting ≤ 2.0 x ULN
3. Alkaline phosphatase < 2.5 x ULN
4. Subjects with biliary stenting do not need to wait for their alkaline
phosphatase to become < 2.5 x ULN if their total bilirubin, AST and ALT have
improved to within required study levels with criteria 12a and 12b
13. Adequate bone marrow function: platelets >100,000 cells/mm3, hemoglobin > 9.0
g/dl and absolute neutrophil count (ANC) >1,500 cells/mm3
14. Adequate renal function: creatinine < 1.5 x ULN, creatinine clearance ≥ 30
mL/min/m2
15. Adequate nutritional state with Albumin ≥ 2.5 g/dL
16. Less than grade 2 pre-existing peripheral neuropathy (per CTCAE)
17. Patients covered by Health Insurance System
Exclusion Criteria:
1. Patients with resectable pancreatic cancer
2. Evidence of the presence of metastases.
3. Patients who have received prior systemic therapy, radiation therapy, or resection
for pancreatic cancer or prior therapy with NP137
4. Patients with known Dihydropyrimidine dehydrogenase (DPD) deficiency, or
homozygosity for UGT1A1*28 polymorphism (UGT1A1 genotype analysis is not required to
be eligible)
5. Previous (within the past 3 years) or concurrent malignancy diagnosis except
non-melanoma skin cancer and in situ carcinomas (excluding in situ breast cancer)
6. History of severe (grade ≥ 3) allergic reactions to one of the components of
chemotherapy, or NP137
7. Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that contraindicates the use of an investigational drug, may
affect the interpretation of the results, may decrease subject's compliance to
study's procedures or may render the patient at high risk from treatment
complications in the opinion of the treating investigator
8. Subjects with known poorly controlled comorbid conditions, including; congestive
heart failure (CHF), chronic obstructive pulmonary disease (COPD), uncontrolled
diabetes mellitus (DM) or neurologic disorders (not acutely related to pancreatic
cancer) or limited function
9. Major surgery within 4 weeks prior to signing informed consent form. Biliary stents
are permitted
10. History of allergy or hypersensitivity to human, humanized or chimeric monoclonal
antibodies
11. History of allergy or hypersensitivity to any of the chemotherapy agents belonging
to mFOLFIRINOX regimen
12. Subjects with a history of chronic HCV, HBV or HIV infection
13. Subjects who have been administered a live vaccine within four weeks prior to the
first administration of therapy
14. Subjects who cannot stop chronic medications that inhibit or induce CYP2C8 or CYP3A4
15. Persons referred to in Articles L1121-5 to L1121-8 of the French code of public
health (this corresponds to all persons protected: pregnant or parturient women,
breastfeeding mothers, persons deprived of liberty by judicial or administrative
decision, persons subject to a legal protection measure)
16. Patients who have active infection requiring systemic therapy (other than HCV, HBV,
HIV).
17. Patients who participate or plan to participate in another interventional clinical
trial or who is in exclusion period for another study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
CHU de GRENOBLE ALPES
Address:
City:
Grenoble
Zip:
38043
Country:
France
Status:
Recruiting
Contact:
Last name:
Gaël ROTH
Phone:
Groth@chu-grenoble.fr
Facility:
Name:
CHU de BORDEAUX
Address:
City:
Bordeaux
Zip:
33404
Country:
France
Status:
Recruiting
Contact:
Last name:
Jean Fredéric BLANC
Facility:
Name:
CHRU Lille
Address:
City:
Lille
Zip:
59037
Country:
France
Status:
Recruiting
Contact:
Last name:
Anthony TURPIN
Facility:
Name:
Hôpital Privé Jean Mermoz
Address:
City:
Lyon
Zip:
69008
Country:
France
Status:
Recruiting
Contact:
Last name:
Pascal ARTRU
Facility:
Name:
AP-HP Pitié Salpetrière
Address:
City:
Paris
Zip:
75013
Country:
France
Status:
Recruiting
Contact:
Last name:
Jean-Baptiste BACHET
Facility:
Name:
CHU Poitiers
Address:
City:
Poitiers
Zip:
86000
Country:
France
Status:
Recruiting
Contact:
Last name:
Camille EVRARD
Facility:
Name:
CHU de REIMS
Address:
City:
Reims
Zip:
51092
Country:
France
Status:
Recruiting
Contact:
Last name:
Olivier BOUCHE
Facility:
Name:
CHU Rennes
Address:
City:
Rennes
Zip:
35033
Country:
France
Status:
Recruiting
Contact:
Last name:
Astrid LIEVRE
Facility:
Name:
CHU St Etienne
Address:
City:
Saint-Étienne
Zip:
42055
Country:
France
Status:
Recruiting
Contact:
Last name:
Nicolas WILLIET
Start date:
March 28, 2023
Completion date:
March 28, 2027
Lead sponsor:
Agency:
University Hospital, Grenoble
Agency class:
Other
Collaborator:
Agency:
NETRIS Pharma
Agency class:
Industry
Source:
University Hospital, Grenoble
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05546853
