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

NCT04005339 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2018-0877
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Advanced Biliary Tract Cancer

Keywords

Advanced Biliary Tract Cancer; Biliary Tract Cancer; GI Cancer; Biliary Cancer; NAPOLI-2

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Overall response rate (ORR).

  6 months

• Median progression-free survival (mPFS).

  6 months

• Median overall survival (mOS).

  6 months

• Median time to disease progression (mTTP).

  6 months

• Disease control rate (DCR).

  6 months

Other Outcomes (2)

• Blood for the analysis of circulating tumor DNA as a surrogate marker of disease burden.

  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.

  6 months

Study Arms (1)

Single Arm

EXPERIMENTAL

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; Drug: Leucovorin; Drug: Fluorouracil

Interventions

Nanoliposomal Irinotecan DRUG

Nanoliposomal irinotecan 70 mg/ IV over 90 minutes, every 14 days

Single Arm

Leucovorin DRUG

Leucovorin 400 mg/ IV over 30 minutes, every 14 days.

Single Arm

Fluorouracil DRUG

Fluorouracil 2,400 mg/m IV over 46 hours.

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Georgetown University: lead
• Ipsen: collaborator

Study Sites (4)

Lombardi Comprehensive Cancer Center, Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Washington University School of Medicine- Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10128, United States

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms; Gastrointestinal Neoplasms

Interventions

irinotecan sucrosofate; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Benjamin Weinberg, MD

  Georgetown University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2019
• First Posted: July 2, 2019
• Study Start: July 29, 2019
• Primary Completion: September 3, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)