A Study of the Safety and Activity of Liposomal Irinotecan in Combination With the 5-FU and Oxaliplatin in the Preoperative Treatment of Pancreatic Adenocarcinoma

A Phase II, Open-label Pilot Study Evaluating the Safety and Activity of Liposomal Irinotecan in Combination With 5-FU and Oxaliplatin in Preoperative Treatment of Pancreatic Adenocarcinoma (NEO-Nal- IRI Study)

This is a phase II, single arm, non-randomized, open label study of liposomal irinotecan with FOLFOX in the neoadjuvant setting in patients with resectable or borderline resectable, previously untreated pancreatic adenocarcinoma. The primary objective of this study is to investigate the safety and feasibility of this treatment regimen in this patient population.

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: Liposomal Irinotecan; Drug: FOLFOX regimen

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alexandra Mueller; Phone Number: (352) 273-9785; Email: PMO@cancer.ufl.edu

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida
    • Orlando, Florida, United States, 32806
      • Orlando Health UF Health Cancer Center
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Memorial Health Care
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Must be at least 18 years of age.
• A new clinical diagnosis of resectable or borderline resectable, previously untreated pancreatic adenocarcinoma confirmed by pathologic specimen evaluation
• No clinical evidence of metastatic disease
• Potentially resectable local disease, as confirmed by CT or MRI of the abdomen
• ECOG performance status of 0 or 1
• Any biliary obstruction must have been treated.
• Subjects with known or suspected Gilbert's disease must be formally tested for UGT1A1*28 with results available to study team prior to treatment initiation

• Adequate organ function; as defined by:

  i. Hematologic-

  1. ANC > 1,500 cells/μl without the use of hematopoietic growth factors; and
  2. Platelet count > 100,000 cells/μl; and

  3. Hemoglobin > 9 g/dL (blood transfusions are permitted for patients with hemoglobin levels below 9 g/dL)

     ii. Hepatic-

  1. Serum total bilirubin within 1.5 x upper limit of normal (ULN) for the institution, with a trend downwards (biliary drainage is allowed for biliary obstruction),

  2. AST and ALT less than or equal to 2.5 x ULN

     iii. Renal- Serum creatinine less than or equal to 1.5 x ULN

     iv. Cardiac- Normal ECG or ECG without any clinically significant findings as defined by the treating physician

• Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 7 months after the last dose of study drug to minimize the risk of pregnancy
• Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 4 months following the last dose of study drug.

Exclusion Criteria:

• A medical history of prior anti-cancer treatment for pancreatic cancer.
• Locally advanced unresectable disease or evidence of metastatic disease.
• Any other invasive malignancy within the past three years.
• Presence of any known contraindications to or hypersensitivities to the investigational products.
• Use of strong CYP3A4 inhibitors or inducers which cannot be discontinued prior to study entry.
• A non-surgical candidate.
• Subject is unable to understand, provide consent or comply with study requirements, treatments or instructions in the opinion of the treating physician.
• Uncontrolled diarrhea, active infection, known interstitial lung disease or other medical condition that precludes safe administration of this combination therapy consistent with manufacturer recommendations.
• Unwilling/unable to comply with birth control requirements while on study.
• Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 7 months for females and 4 months for males after the last dose of study drug.
• Females who are pregnant or breastfeeding.
• History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician.
• Prisoners or subjects who are involuntarily incarcerated.
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.
• Subjects demonstrating an inability to comply with the study and/or follow-up procedures.
• Known dihydrypyrimidine (DPD) deficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liposomal irinotecan with FOLFOX; Subjects will receive 8 cycles and each cycle is 14 days.	Drug: Liposomal Irinotecan; Subjects will receive 60 mg/m2 intravenously on Day 1 of each 14 day cycle.; Other Names: ONIVYDE; Drug: FOLFOX regimen; Subjects will receive FOLFOX (oxaliplatin 60 mg/m2 IV, leucovorin 400 mg/m2 IV, and 5-fluorouracil 2400 mg/m2 IV) on Day 1 of each 14 day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30 day post operative complication rate	To determine the 30 day post operative complication rate, as measured by hospital readmission, death, second surgery or interventional procedure, or major complications extending hospital stay	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Completion Rate	To determine the treatment completion rate of therapy, as defined by the percentage of subjects that completed all intended cycles	4 months
Rate of complete surgical resection	To determine the rate of complete surgical resection (R0)	7 months
Objective Response Rate	To determine radiographic objective response rate of the primary tumor as measured by RECIST v 1.1 criteria	5 months
Biochemical Response Rate	To determine the biochemical response rate and pattern of response as measured by serial CA 19-9 levels	9 months
Patient-Reported Quality of Life	To determine the patient-reported quality of life during treatment as measured by the NCI validated FACT-G survey	9 months
Rate of other pathologic downstaging	To determine the rate of other pathologic downstaging	7 months
To determine the safety of liposomal irinotecan in combination with 5-fluorouracil, oxaliplatin, and leucovorin as assessed by the number of treatment-related adverse events as assessed by CTCAE v 4.0		9 months

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Ipsen
• Investigators: Principal Investigator: Thomas George, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2018
• Primary Completion (Actual): September 16, 2023
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: March 12, 2018
• First Submitted That Met QC Criteria: March 28, 2018
• First Posted (Actual): March 29, 2018

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: neoadjuvant; chemotherapy; pancreatic adenocarcinoma; resectable; borderline resectable; ONIVYDE
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: UF-STO-PANC-004; IRB201800866 -A (Other Identifier: University of Florida); OCR16281 (Other Identifier: UF OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No