- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03528785
A Study of Nal-IRI With 5-FU, Levofolinic Acid and Oxaliplatin in Patients With Resectable Pancreatic Cancer (nITRo)
A Phase II Study of Liposomial IrinoTecan (Nal-IRI) With 5-Fluorouracil, Levofolinic Acid and Oxaliplatin in Patients With Resectable Pancreatic Cancer "nITRo Trial
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: stefano Milleri, Dr
- Phone Number: +390458126619
- Email: stefano.milleri@crc.vr.it
Study Locations
-
-
-
Verona, Italy, 37134
- Recruiting
- Centro Ricerche Cliniche
-
Contact:
- Stefano Milleri, Dr.
- Phone Number: +390458126619
- Email: stefano.milleri@crc.vr.it
-
Contact:
- Giorgia Barbiero, Dr.
- Phone Number: +390458126562
- Email: giorgia.barbiero@crc.vr.it
-
Principal Investigator:
- Davide Melisi, Dr
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Single Arm
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.
|
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Number of patients achieving R0 resection after preoperative nanoliposomal irinotecan (nal-IRI), Oxaliplatin, Leucovorin (LV), 5-FluoroUracil (5-FU)
|
4-8 weeks after the completion of 3 courses of treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To determine 2-year overall survival (OS)
Time Frame: 2 years
|
(OS)
|
2 years
|
determine disease-free survival (DFS)
Time Frame: through study completion, an average of 2 years
|
(DFS)
|
through study completion, an average of 2 years
|
estimate frequency and severity of adverse events associated with chemotherapy
Time Frame: through study completion, an average of 2 years
|
AE
|
through study completion, an average of 2 years
|
determine overall response rate (ORR) following preoperative chemotherapy
Time Frame: through study completion, an average of 2 years
|
ORR
|
through study completion, an average of 2 years
|
estimate proportion of patients going to surgery for resection after preoperative chemotherapy
Time Frame: through study completion, an average of 2 years
|
estimate proportion of patients going to surgery for resection after preoperative chemotherapy
|
through study completion, an average of 2 years
|
estimate pathologic response rate (pCR)
Time Frame: through study completion, an average of 2 years
|
(pCR)
|
through study completion, an average of 2 years
|
assess lymph node status
Time Frame: through study completion, an average of 2 years
|
assess lymph node status
|
through study completion, an average of 2 years
|
assess surgical mortality
Time Frame: through study completion, an average of 2 years
|
assess surgical mortality
|
through study completion, an average of 2 years
|
assess surgical morbidity
Time Frame: through study completion, an average of 2 years
|
assess surgical morbidity
|
through study completion, an average of 2 years
|
Collaborators and Investigators
Investigators
- Study Director: stefano milleri, Dr, Centro Ricerche Cliniche
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Endocrine System Diseases
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Pancreatic Diseases
- Adenocarcinoma
- Pancreatic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protective Agents
- Topoisomerase Inhibitors
- Micronutrients
- Vitamins
- Topoisomerase I Inhibitors
- Antidotes
- Vitamin B Complex
- Oxaliplatin
- Leucovorin
- Irinotecan
- Levoleucovorin
Other Study ID Numbers
- CRC2017_01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Supporting Information Type
- Study Protocol
- Clinical Study Report (CSR)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Pancreatic Adenocarcinoma
-
Fudan UniversityUnknownStage IA Pancreatic Adenocarcinoma | Stage IB Pancreatic Adenocarcinoma | Stage IIA Pancreatic Adenocarcinoma | Stage IIB Pancreatic AdenocarcinomaChina
-
Roswell Park Cancer InstituteNot yet recruitingStage II Pancreatic Cancer AJCC v8 | Stage III Pancreatic Cancer AJCC v8 | Stage IV Pancreatic Cancer AJCC v8 | Metastatic Pancreatic Ductal Adenocarcinoma | Locally Advanced Pancreatic Ductal Adenocarcinoma | Advanced Pancreatic Ductal Adenocarcinoma | Unresectable Pancreatic Ductal Adenocarcinoma and other conditionsUnited States
-
Xian-Jun YuCompletedStage IA Pancreatic Adenocarcinoma | Stage IB Pancreatic Adenocarcinoma | Stage IIA Pancreatic Adenocarcinoma | Stage IIB Pancreatic AdenocarcinomaChina
-
Xian-Jun YuCompletedStage IA Pancreatic Adenocarcinoma | Stage IB Pancreatic Adenocarcinoma | Stage IIA Pancreatic Adenocarcinoma | Stage IIB Pancreatic AdenocarcinomaChina
-
Scandion Oncology A/SAlcedis GmbHRecruitingMetastatic Pancreatic Adenocarcinoma | Locally Advanced Pancreatic Adenocarcinoma | Inoperable Disease | Localized Pancreatic AdenocarcinomaDenmark, Germany
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingBorderline Resectable Pancreatic Adenocarcinoma | Resectable Pancreatic Ductal Adenocarcinoma | Locally Advanced Pancreatic Ductal AdenocarcinomaUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)RecruitingPancreas Adenocarcinoma | Locally Advanced Pancreatic Adenocarcinoma | Borderline Resectable Pancreatic AdenocarcinomaUnited States
-
Memorial Sloan Kettering Cancer CenterRecruitingPancreatic Cancer | Pancreatic Cancer Metastatic | Pancreatic Cancer Stage IV | Metastatic Pancreatic Carcinoma | Metastatic Pancreatic Adenocarcinoma | Pancreatic Carcinoma | Metastatic Pancreatic Cancer | Pancreatic Cancer Non-resectable | Metastatic Pancreatic Ductal Adenocarcinoma | Pancreatic Carcinoma... and other conditionsUnited States
-
Lawson Health Research InstituteLondon Health Sciences FoundationNot yet recruitingBorderline Resectable Pancreatic Adenocarcinoma | Resectable Pancreatic Adenocarcinoma
-
Jean-Luc Van LaethemCelgene CorporationCompletedPancreatic Adenocarcinoma Resectable | Pancreatic Adenocarcinoma Metastatic | Pancreatic Adenocarcinoma Locally AdvancedBelgium
Clinical Trials on Irinotecan Liposomal Injection [Onivyde]; oxaliplatin, 5-FU; Levofolinic Acid
-
University of CologneServierRecruitingPancreatic Cancer | Surgery | Metastasis | Oligometastatic DiseaseGermany
-
Ludwig-Maximilians - University of MunichActive, not recruiting
-
Changhoon YooUlsan University Hospital; Inje University; Kyungpook National University Chilgok... and other collaboratorsCompletedMetastatic Biliary Tract CancerKorea, Republic of
-
Dominik Paul ModestGerman Research Foundation; Institut für Klinische Krebsforschung IKF GmbH...Recruiting
-
Wakayama Medical UniversityCompletedPatients With Borderline Resectable Pancreatic CancerJapan
-
IpsenRecruitingMetastatic Pancreatic AdenocarcinomaSpain, France, Italy, Hungary, Australia, Germany, Portugal
-
OncoSil Medical LimitedRecruitingLocally Advanced Pancreatic CancerSpain, Belgium, United Kingdom, Italy, Australia
-
Federation Francophone de Cancerologie DigestiveRecruiting
-
AIO-Studien-gGmbHServier Deutschland GmbH; Crolll GmbhActive, not recruitingMetastatic Pancreatic Cancer | Locally Advanced Pancreatic CancerGermany
-
Zhejiang UniversityNot yet recruitingResectable Pancreatic Cancer | Neoadjuvant Chemotherapy