Back to resultsA Study of Nal-IRI With 5-FU, Levofolinic Acid and Oxaliplatin in Patients With Resectable Pancreatic Cancer (nITRo)
Primary Purpose
Pancreatic Adenocarcinoma
Status
Unknown status
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Irinotecan Liposomal Injection [Onivyde]; oxaliplatin, 5-FU; Levofolinic Acid
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Adenocarcinoma focused on measuring Pancreatic Adenocarcinoma, Liposomial IrinoTecan, nal-IRI, Resectable pancreatic cancer
Eligibility Criteria
Inclusion Criteria:
- Able to understand and provide written informed consent.
- ≥ 18 years of age.
- Histologically or cytologically confirmed adenocarcinoma of exocrine pancreas.
- Patients must have measurable disease in the pancreas, with no evidence of metastatic disease on imaging of the chest, abdomen and pelvis (contrast-enhanced CT or MRI abdomen with contrast instead of abdominal CT); PET scans alone will not be adequate alternatives.
The primary tumor must be surgically resectable, defined as:
- no involvement (abutment or encasement) of the major arteries (celiac, common hepatic and/or superior mesenteric artery);
- no involvement or <180° interface between tumor and vessel wall of the portal vein, superior mesenteric vein and/or portal vein/splenic vein confluence.
- Adequate hepatic, renal and hematological function.
Exclusion Criteria:
- Serum total bilirubin ≥2 x ULN (biliary drainage is allowed for biliary obstruction).
- Severe renal impairment (CLcr ≤ 30 ml/min).
- Inadequate bone marrow reserves as evidenced by:
- ANC ≤ 1,500 cells/μl; or Platelet count ≤ 100,000 cells/μl; or Hemoglobin ≤ 9 g/dL
- KPS < 60
- Patients who received previous chemotherapy or radiotherapy for pancreatic disease.
- Any clinically significant disorder impacting the risk-benefit balance negatively per physician's judgment.
- Any clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 2.
- Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months.
- NYHA Class III or IV congestive heart failure, ventricular
Sites / Locations
- Centro Ricerche ClinicheRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single Arm
Arm Description
All patients will receive a treatment scheme of Irinotecan Liposomal Injection [Onivyde], oxaliplatin, Levofolinic Acid and 5-fluorouracil (5 -FU) on Day 1 and Day 15 of each 28 day cycles.
Outcomes
Primary Outcome Measures
Number of patients achieving R0 resection after preoperative nanoliposomal irinotecan (nal-IRI), Oxaliplatin, Leucovorin (LV), 5-FluoroUracil (5-FU)
Number of patients achieving R0 resection after preoperative nanoliposomal irinotecan (nal-IRI), Oxaliplatin, Leucovorin (LV), 5-FluoroUracil (5-FU)
Secondary Outcome Measures
To determine 2-year overall survival (OS)
(OS)
determine disease-free survival (DFS)
(DFS)
estimate frequency and severity of adverse events associated with chemotherapy
AE
determine overall response rate (ORR) following preoperative chemotherapy
ORR
estimate proportion of patients going to surgery for resection after preoperative chemotherapy
estimate proportion of patients going to surgery for resection after preoperative chemotherapy
estimate pathologic response rate (pCR)
(pCR)
assess lymph node status
assess lymph node status
assess surgical mortality
assess surgical mortality
assess surgical morbidity
assess surgical morbidity
Full Information
NCT ID
NCT03528785
First Posted
November 9, 2017
Last Updated
July 27, 2021
Sponsor
Centro Ricerche Cliniche di Verona
1. Study Identification
Unique Protocol Identification Number
NCT03528785
Brief Title
A Study of Nal-IRI With 5-FU, Levofolinic Acid and Oxaliplatin in Patients With Resectable Pancreatic Cancer
Acronym
nITRo
Official Title
A Phase II Study of Liposomial IrinoTecan (Nal-IRI) With 5-Fluorouracil, Levofolinic Acid and Oxaliplatin in Patients With Resectable Pancreatic Cancer "nITRo Trial
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Unknown status
Study Start Date
March 2, 2018 (Actual)
Primary Completion Date
November 15, 2021 (Anticipated)
Study Completion Date
November 1, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centro Ricerche Cliniche di Verona
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Rational:Pancreatic cancer is a systemic disease at the time of diagnosis, even among patients with apparent localized disease. Surgical resection is the only potentially curative therapy for pancreatic cancer, but in patients who undergo surgery and postoperative therapy, metastatic relapse remains common and no more than 20% of patients achieve 5-year survival.
Because of this aggressive biologic behavior, an increasing interest is growing about preoperative treatments in resectable pancreatic cancer.
The combination chemotherapeutic regimen with irinotecan + 5-fluorouracil (5-FU)/leucovorin (LV) + oxaliplatin (FOLFIRINOX) is an effective choice for first line treatment in patients affected by advanced pancreatic cancer, and in this setting it achieved a Disease Control Rate of 70.2 % (10). In this regard, FOLFIRINOX is currently explored as preoperative regimen in a number of clinical trials in resectable pancreatic cancer.
A critical challenge in this field remains the introduction in these combination treatments of the most novel and effective agents such as nalIRI, in order to obtain a more profound tumor shrinkage, to increase the rate of R0 resections, to allow an early treatment of occult micrometastatic disease, and eventually, to improve survival in patients with resectable pancreatic cancer.
This study proposal is designed to address this challenge. Preliminary results, collected during the Part 1 Dose Escalation of a current clinical trial performed in mPDAC, show that dose of nal-IRI: 60 mg/m2, Oxaliplatin: 60 mg/m2, 5-FU/LV: 2400/400 mg/m2 is safe.
Detailed Description
This is a study to determine the proportion of patients affected by resectable pancreatic cancer who achieve R0 resection after a perioperative 6-cycle chemotherapy, 3 pre- and 3 post-surgery, in the absence of disease progression or unacceptable toxicity.
All patients in the program will be identified by a unique identifier number assigned sequentially.
Patients will receive a treatment scheme of nal-IRI, oxaliplatin, Levofolinic Acid and 5-fluorouracil (5 -FU) on Day 1 and Day 15 of each 28 day cycles.
C1D1 is a fixed day, C1D15 and Day 1 and Day 15 of all subsequent cycles should be performed with a window of ± 2 days.
Patients achieving stable disease or better will undergo pancreatectomy 4-8 weeks after completion of first 3 courses of treatment. Within 4-8 weeks following pancreatectomy, patients will receive an additional 3 cycles of nal-IRI, oxaliplatin, Levofolinic Acid and 5-fluorouracil (5 -FU) treatment in the absence of disease progression or unacceptable toxicity.
Tumor responses will be assessed after 3 cycles of preoperative treatment and after 3 cycles of postoperative treatment or sooner if the treating physician suspects disease progression based on clinical signs and symptoms. All treatment decisions will be based on the local radiologist and/or treating physician assessment of disease status.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Adenocarcinoma
Keywords
Pancreatic Adenocarcinoma, Liposomial IrinoTecan, nal-IRI, Resectable pancreatic cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
67 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Single Arm
Arm Type
Experimental
Arm Description
All patients will receive a treatment scheme of Irinotecan Liposomal Injection [Onivyde], oxaliplatin, Levofolinic Acid and 5-fluorouracil (5 -FU) on Day 1 and Day 15 of each 28 day cycles.
Intervention Type
Drug
Intervention Name(s)
Irinotecan Liposomal Injection [Onivyde]; oxaliplatin, 5-FU; Levofolinic Acid
Intervention Description
Oxaliplatin 60 mg/m2 IV in 120 minutes) on Days 1 and 15 of each cycle
Irinotecan Liposomal Injection [Onivyde] (60 mg/m2 IV over 90 minutes) on Days 1 and 15 of each cycle
Levofolinic acid (200 mg/m2 IV over 30 minutes) on Days 1 and 15 of each cycle
5FU (2.400 mg/m2 IV over 46 hours) on Days 1 and 15 of each cycle
Primary Outcome Measure Information:
Title
Number of patients achieving R0 resection after preoperative nanoliposomal irinotecan (nal-IRI), Oxaliplatin, Leucovorin (LV), 5-FluoroUracil (5-FU)
Description
Number of patients achieving R0 resection after preoperative nanoliposomal irinotecan (nal-IRI), Oxaliplatin, Leucovorin (LV), 5-FluoroUracil (5-FU)
Time Frame
4-8 weeks after the completion of 3 courses of treatment
Secondary Outcome Measure Information:
Title
To determine 2-year overall survival (OS)
Description
(OS)
Time Frame
2 years
Title
determine disease-free survival (DFS)
Description
(DFS)
Time Frame
through study completion, an average of 2 years
Title
estimate frequency and severity of adverse events associated with chemotherapy
Description
AE
Time Frame
through study completion, an average of 2 years
Title
determine overall response rate (ORR) following preoperative chemotherapy
Description
ORR
Time Frame
through study completion, an average of 2 years
Title
estimate proportion of patients going to surgery for resection after preoperative chemotherapy
Description
estimate proportion of patients going to surgery for resection after preoperative chemotherapy
Time Frame
through study completion, an average of 2 years
Title
estimate pathologic response rate (pCR)
Description
(pCR)
Time Frame
through study completion, an average of 2 years
Title
assess lymph node status
Description
assess lymph node status
Time Frame
through study completion, an average of 2 years
Title
assess surgical mortality
Description
assess surgical mortality
Time Frame
through study completion, an average of 2 years
Title
assess surgical morbidity
Description
assess surgical morbidity
Time Frame
through study completion, an average of 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Able to understand and provide written informed consent.
≥ 18 years of age.
Histologically or cytologically confirmed adenocarcinoma of exocrine pancreas.
Patients must have measurable disease in the pancreas, with no evidence of metastatic disease on imaging of the chest, abdomen and pelvis (contrast-enhanced CT or MRI abdomen with contrast instead of abdominal CT); PET scans alone will not be adequate alternatives.
The primary tumor must be surgically resectable, defined as:
no involvement (abutment or encasement) of the major arteries (celiac, common hepatic and/or superior mesenteric artery);
no involvement or <180° interface between tumor and vessel wall of the portal vein, superior mesenteric vein and/or portal vein/splenic vein confluence.
Adequate hepatic, renal and hematological function.
Exclusion Criteria:
Serum total bilirubin ≥2 x ULN (biliary drainage is allowed for biliary obstruction).
Severe renal impairment (CLcr ≤ 30 ml/min).
Inadequate bone marrow reserves as evidenced by:
ANC ≤ 1,500 cells/μl; or Platelet count ≤ 100,000 cells/μl; or Hemoglobin ≤ 9 g/dL
KPS < 60
Patients who received previous chemotherapy or radiotherapy for pancreatic disease.
Any clinically significant disorder impacting the risk-benefit balance negatively per physician's judgment.
Any clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 2.
Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months.
NYHA Class III or IV congestive heart failure, ventricular
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
stefano Milleri, Dr
Phone
+390458126619
Email
stefano.milleri@crc.vr.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
stefano milleri, Dr
Organizational Affiliation
centro ricerche cliniche
Official's Role
Study Director
Facility Information:
Facility Name
Centro Ricerche Cliniche
City
Verona
ZIP/Postal Code
37134
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefano Milleri, Dr.
Phone
+390458126619
Email
stefano.milleri@crc.vr.it
First Name & Middle Initial & Last Name & Degree
Giorgia Barbiero, Dr.
Phone
+390458126562
Email
giorgia.barbiero@crc.vr.it
First Name & Middle Initial & Last Name & Degree
Davide Melisi, Dr
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
all IPDs published
IPD Sharing Time Frame
starting 6 months after publication
Citations:
PubMed Identifier
33403007
Citation
Simionato F, Zecchetto C, Merz V, Cavaliere A, Casalino S, Gaule M, D'Onofrio M, Malleo G, Landoni L, Esposito A, Marchegiani G, Casetti L, Tuveri M, Paiella S, Scopelliti F, Giardino A, Frigerio I, Regi P, Capelli P, Gobbo S, Gabbrielli A, Bernardoni L, Fedele V, Rossi I, Piazzola C, Giacomazzi S, Pasquato M, Gianfortone M, Milleri S, Milella M, Butturini G, Salvia R, Bassi C, Melisi D. A phase II study of liposomal irinotecan with 5-fluorouracil, leucovorin and oxaliplatin in patients with resectable pancreatic cancer: the nITRO trial. Ther Adv Med Oncol. 2020 Sep 4;12:1758835920947969. doi: 10.1177/1758835920947969. eCollection 2020.
Results Reference
derived
Learn more about this trial
A Study of Nal-IRI With 5-FU, Levofolinic Acid and Oxaliplatin in Patients With Resectable Pancreatic Cancer
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