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

Primary Purpose

Advanced Biliary Tract Cancer

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nanoliposomal Irinotecan
Leucovorin
Fluorouracil
Sponsored by
Georgetown University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Biliary Tract Cancer focused on measuring Advanced Biliary Tract Cancer, Biliary Tract Cancer, GI Cancer, Biliary Cancer, NAPOLI-2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Lombardi Comprehensive Cancer Center, Georgetown UniversityRecruiting
  • Indiana University Health Melvin and Bren Simon Cancer CenterRecruiting
  • Washington University School of Medicine- Siteman Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single Arm

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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).
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).
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).
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).
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).
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).
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.

Full Information

First Posted
June 27, 2019
Last Updated
January 5, 2023
Sponsor
Georgetown University
Collaborators
Ipsen
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1. Study Identification

Unique Protocol Identification Number
NCT04005339
Brief Title
NAPOLI-2: Fluorouracil, Leucovorin, and Nanoliposomal Irinotecan in Biliary Cancer
Official Title
NAPOLI-2: Phase II Study of Fluorouracil, Leucovorin, and Nanoliposomal Irinotecan in Previously Treated Advanced Biliary Tract Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 29, 2019 (Actual)
Primary Completion Date
November 30, 2023 (Anticipated)
Study Completion Date
July 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Georgetown University
Collaborators
Ipsen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Biliary Tract Cancer
Keywords
Advanced Biliary Tract Cancer, Biliary Tract Cancer, GI Cancer, Biliary Cancer, NAPOLI-2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single Arm
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Nanoliposomal Irinotecan
Intervention Description
Nanoliposomal irinotecan 70 mg/ IV over 90 minutes, every 14 days
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Intervention Description
Leucovorin 400 mg/ IV over 30 minutes, every 14 days.
Intervention Type
Drug
Intervention Name(s)
Fluorouracil
Intervention Description
Fluorouracil 2,400 mg/m IV over 46 hours.
Primary Outcome Measure Information:
Title
The efficacy of fluorouracil, leucovorin, and nanoliposomal irinotecan in advanced biliary tract cancers following progression on or intolerance of gemcitabine and platinum chemotherapy.
Description
Defined as positive if there is no evidence of disease progression (PD) at 4 months, as measured by RECIST v1.1 criteria
Time Frame
4 months
Secondary Outcome Measure Information:
Title
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.
Description
Measured in terms of best overall response rate (ORR).
Time Frame
6 months
Title
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.
Description
Measured in terms of median progression-free survival (mPFS).
Time Frame
6 months
Title
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.
Description
Measured in terms of median overall survival (mOS).
Time Frame
6 months
Title
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.
Description
Measured in terms of median time to disease progression (mTTP).
Time Frame
6 months
Title
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.
Description
Measured in terms of disease control rate (DCR).
Time Frame
6 months
Title
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.
Description
Measured in terms of median duration of disease control (DDC).
Time Frame
6 months
Title
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.
Description
Measured in terms of maximum change in tumor marker, CA19-9.
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Blood for the analysis of circulating tumor DNA as a surrogate marker of disease burden.
Description
Correlation of dynamics of circulating tumor DNA change compared with change in CA19-9.
Time Frame
6 months
Title
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.
Description
Correlation of tumor genetic mutations and protein expression levels with progression-free survival.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benjamin Weinberg, MD
Organizational Affiliation
Georgetown University
Official's Role
Study Chair
Facility Information:
Facility Name
Lombardi Comprehensive Cancer Center, Georgetown University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yael Meirovich
Phone
202-687-9861
Email
ym419@georgetown.edu
First Name & Middle Initial & Last Name & Degree
Benjamin Weinberg, MD
Facility Name
Indiana University Health Melvin and Bren Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Martinez
Phone
317-274-3502
Email
maimart@iu.edu
First Name & Middle Initial & Last Name & Degree
Anita Turk, MD
Facility Name
Washington University School of Medicine- Siteman Cancer Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kelsey Brodbeck
Phone
314-747-8085
Email
bkelsey@wustl.edu
First Name & Middle Initial & Last Name & Degree
Katrina Pedersen, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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