A Study of Nal-IRI With 5-FU, Levofolinic Acid and Oxaliplatin in Patients With Resectable Pancreatic Cancer (nITRo)

July 27, 2021 updated by: Centro Ricerche Cliniche di Verona

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

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

Interventional

Enrollment (Anticipated)

67

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Verona, Italy, 37134
        • Recruiting
        • Centro Ricerche Cliniche
        • Contact:
        • Contact:
        • Principal Investigator:
          • Davide Melisi, Dr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Able to understand and provide written informed consent.
  2. ≥ 18 years of age.
  3. Histologically or cytologically confirmed adenocarcinoma of exocrine pancreas.
  4. 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.
  5. The primary tumor must be surgically resectable, defined as:

    1. no involvement (abutment or encasement) of the major arteries (celiac, common hepatic and/or superior mesenteric artery);
    2. no involvement or <180° interface between tumor and vessel wall of the portal vein, superior mesenteric vein and/or portal vein/splenic vein confluence.
  6. Adequate hepatic, renal and hematological function.

Exclusion Criteria:

  1. Serum total bilirubin ≥2 x ULN (biliary drainage is allowed for biliary obstruction).
  2. Severe renal impairment (CLcr ≤ 30 ml/min).
  3. Inadequate bone marrow reserves as evidenced by:
  4. ANC ≤ 1,500 cells/μl; or Platelet count ≤ 100,000 cells/μl; or Hemoglobin ≤ 9 g/dL
  5. KPS < 60
  6. Patients who received previous chemotherapy or radiotherapy for pancreatic disease.
  7. Any clinically significant disorder impacting the risk-benefit balance negatively per physician's judgment.
  8. Any clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 2.
  9. Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months.
  10. NYHA Class III or IV congestive heart failure, ventricular

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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.
  • 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

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

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: stefano milleri, Dr, Centro Ricerche Cliniche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2018

Primary Completion (Anticipated)

November 15, 2021

Study Completion (Anticipated)

November 1, 2022

Study Registration Dates

First Submitted

November 9, 2017

First Submitted That Met QC Criteria

May 17, 2018

First Posted (Actual)

May 18, 2018

Study Record Updates

Last Update Posted (Actual)

August 2, 2021

Last Update Submitted That Met QC Criteria

July 27, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

all IPDs published

IPD Sharing Time Frame

starting 6 months after publication

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

No

Studies a U.S. FDA-regulated device product

No

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.

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