NAPOLI-2: Fluorouracil, Leucovorin, and Nanoliposomal Irinotecan in Biliary Cancer

NAPOLI-2: Phase II Study of Fluorouracil, Leucovorin, and Nanoliposomal Irinotecan in Previously Treated Advanced Biliary Tract Cancer

This is a study to evaluate the clinical activity of the combination of fluorouracil, leucovorin, and nanoliposomal irinotecan as second-line treatment in patients with advanced biliary tract cancers following gemcitabine and platinum chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Advanced Biliary Tract Cancer
• Intervention / Treatment: Drug: Nanoliposomal Irinotecan; Drug: Leucovorin; Drug: Fluorouracil

Detailed Description

This is a single arm, open label, multicenter phase II study to evaluate the clinical activity of the combination of fluorouracil, leucovorin, and nanoliposomal irinotecan as second-line treatment in patients with advanced biliary tract cancers following gemcitabine and platinum chemotherapy. Patients with advanced biliary tract cancers who have adequate performance status and adequate hepatic and renal function will be eligible. Patients may have received adjuvant chemotherapy and/or radiation therapy prior to enrolling in the trial, but a minimum of 6 months between adjuvant chemotherapy and this current therapy are required. Patients may continue on study as long as they are tolerating treatment and do not have progression of disease by RECIST v1.1 criteria. Response assessments will occur using imaging (CT or MRI) every 8 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Recruiting
      • Lombardi Comprehensive Cancer Center, Georgetown University
      • Contact: Princess Jones; Phone Number: 202-687-3091; Email: paj24@georgetown.edu
      • Principal Investigator: Benjamin Weinberg, MD
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Active, not recruiting
      • Indiana University Health Melvin and Bren Simon Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Active, not recruiting
      • Washington University School of Medicine- Siteman Cancer Center
  • New York
    • New York, New York, United States, 10128
      • Active, not recruiting
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pathologically-confirmed biliary tract cancer (cholangiocarcinoma or gallbladder adenocarcinoma), unresectable or metastatic
• Disease progression on or intolerance of gemcitabine- and platinum-based chemotherapy
• No more than 1 prior line of chemotherapy for unresectable or metastatic disease (adjuvant therapy does not count)
• Measurable disease by RECIST v1.1 criteria
• ECOG performance status of 0-1
• At least 18 years of age
• HIV-positive patients are eligible provided: Stable HAART regimen, No concurrent prophylactic antibiotics or antifungals, and CD4 count above 250 and undetectable viral load
• Adequate bone marrow, hepatic, and renal function
• Consent to access archived tumor tissue if available (available tissue is not required for enrollment)

Exclusion Criteria:

• Ampullary adenocarcinoma
• Woman who are pregnant or breastfeeding
• Anti-cancer treatment within 3 weeks prior to enrollment
• Prior irinotecan or nanoliposomal irinotecan
• Central nervous system metastases unless stable for at least 4 weeks and at least 2 weeks off corticosteroids
• Exposure to a strong CYP3A4 inducer, strong CYP3A4 inhibitor, or strong UGT1A1 inhibitor within 2 weeks of study start
• Known concurrent malignancy or other malignancy within 3 years except for non-melanomatous skin cancers, prostate or cervical cancers following curative therapy, or superficial bladder cancer
• Bowel obstruction
• Allergy or hypersensitivity to fluoropyrimidines, irinotecan, or nanoliposomal irinotecan
• Clinically significant liver disease: Patients with resolved hepatitis B infection are eligible if HBsAg testing is negative; Patients with resolved hepatitis C infection are eligible if viral RNA PCR is negative
• Severe infections within 4 weeks prior to enrollment
• Major surgery within 4 weeks prior to enrollment

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: Single Arm; Nanoliposomal irinotecan 70 mg/ IV over 90 minutes, every 14 days. Leucovorin 400 mg/ IV over 30 minutes, every 14 days. Fluorouracil 2,400 mg/m IV over 46 hours.	Drug: Nanoliposomal Irinotecan; Nanoliposomal irinotecan 70 mg/ IV over 90 minutes, every 14 days; Drug: Leucovorin; Leucovorin 400 mg/ IV over 30 minutes, every 14 days.; Drug: Fluorouracil; Fluorouracil 2,400 mg/m IV over 46 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The efficacy of fluorouracil, leucovorin, and nanoliposomal irinotecan in advanced biliary tract cancers following progression on or intolerance of gemcitabine and platinum chemotherapy.	Defined as positive if there is no evidence of disease progression (PD) at 4 months, as measured by RECIST v1.1 criteria	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR).	The activity of fluorouracil, leucovorin, and nanoliposomal irinotecan in patients with advanced biliary tract cancers treated following progression on or intolerance of gemcitabine and platinum chemotherapy measured in terms of best overall response rate (ORR).	6 months
Median progression-free survival (mPFS).	The activity of fluorouracil, leucovorin, and nanoliposomal irinotecan in patients with advanced biliary tract cancers treated following progression on or intolerance of gemcitabine and platinum chemotherapy measured in terms of median progression-free survival (mPFS).	6 months
Median overall survival (mOS).	The activity of fluorouracil, leucovorin, and nanoliposomal irinotecan in patients with advanced biliary tract cancers treated following progression on or intolerance of gemcitabine and platinum chemotherapy measured in terms of median overall survival (mOS).	6 months
Median time to disease progression (mTTP).	The activity of fluorouracil, leucovorin, and nanoliposomal irinotecan in patients with advanced biliary tract cancers treated following progression on or intolerance of gemcitabine and platinum chemotherapy measured in terms of median time to disease progression (mTTP).	6 months
Disease control rate (DCR).	The activity of fluorouracil, leucovorin, and nanoliposomal irinotecan in patients with advanced biliary tract cancers treated following progression on or intolerance of gemcitabine and platinum chemotherapy measured in terms of disease control rate (DCR).	6 months
Median duration of disease control (DDC).	The activity of fluorouracil, leucovorin, and nanoliposomal irinotecan in patients with advanced biliary tract cancers treated following progression on or intolerance of gemcitabine and platinum chemotherapy measured in terms of median duration of disease control (DDC).	6 months
Maximum change in tumor marker, CA19-9.	The activity of fluorouracil, leucovorin, and nanoliposomal irinotecan in patients with advanced biliary tract cancers treated following progression on or intolerance of gemcitabine and platinum chemotherapy measured in terms of maximum change in tumor marker, CA19-9.	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood for the analysis of circulating tumor DNA as a surrogate marker of disease burden.	Correlation of dynamics of circulating tumor DNA change compared with change in CA19-9.	6 months
Archived tumor tissue using next-generation sequencing (NGS) and immunohistochemistry (IHC) in order to elucidate potential mutational biomarkers predictive of response to fluorouracil, leucovorin, and nanoliposomal irinotecan.	Correlation of tumor genetic mutations and protein expression levels with progression-free survival.	6 months

Collaborators and Investigators

• Sponsor: Georgetown University
• Collaborators: Ipsen
• Investigators: Study Chair: Benjamin Weinberg, MD, Georgetown University

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2019
• Primary Completion (Estimated): May 30, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: June 27, 2019
• First Submitted That Met QC Criteria: June 28, 2019
• First Posted (Actual): July 2, 2019

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Advanced Biliary Tract Cancer; Biliary Tract Cancer; GI Cancer; Biliary Cancer; NAPOLI-2
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Irinotecan
• Other Study ID Numbers: 2018-0877

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