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

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ClinicalTrials.gov Identifier: NCT04005339
Recruitment Status : Recruiting
First Posted : July 2, 2019
Last Update Posted : December 22, 2023
Sponsor:
Collaborator:
Ipsen
Information provided by (Responsible Party):
Georgetown University

Study Description
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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.

Condition or disease Intervention/treatment Phase
Advanced Biliary Tract Cancer Drug: Nanoliposomal Irinotecan Drug: Leucovorin Drug: Fluorouracil Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: NAPOLI-2: Phase II Study of Fluorouracil, Leucovorin, and Nanoliposomal Irinotecan in Previously Treated Advanced Biliary Tract Cancer
Actual Study Start Date : July 29, 2019
Estimated Primary Completion Date : May 30, 2024
Estimated Study Completion Date : July 31, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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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.


Outcome Measures
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Primary Outcome Measures :
  1. The efficacy of fluorouracil, leucovorin, and nanoliposomal irinotecan in advanced biliary tract cancers following progression on or intolerance of gemcitabine and platinum chemotherapy. [ Time Frame: 4 months ]
    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 :
  1. Overall response rate (ORR). [ Time Frame: 6 months ]
    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).

  2. Median progression-free survival (mPFS). [ Time Frame: 6 months ]
    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).

  3. Median overall survival (mOS). [ Time Frame: 6 months ]
    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).

  4. Median time to disease progression (mTTP). [ Time Frame: 6 months ]
    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).

  5. Disease control rate (DCR). [ Time Frame: 6 months ]
    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. Median duration of disease control (DDC). [ Time Frame: 6 months ]
    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).

  7. Maximum change in tumor marker, CA19-9. [ Time Frame: 6 months ]
    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.


Other Outcome Measures:
  1. Blood for the analysis of circulating tumor DNA as a surrogate marker of disease burden. [ Time Frame: 6 months ]
    Correlation of dynamics of circulating tumor DNA change compared with change in CA19-9.

  2. 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. [ Time Frame: 6 months ]
    Correlation of tumor genetic mutations and protein expression levels with progression-free survival.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04005339


Locations
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United States, District of Columbia
Lombardi Comprehensive Cancer Center, Georgetown University Recruiting
Washington, District of Columbia, United States, 20007
Contact: Princess Jones    202-687-3091    paj24@georgetown.edu   
Principal Investigator: Benjamin Weinberg, MD         
United States, Indiana
Indiana University Health Melvin and Bren Simon Cancer Center Active, not recruiting
Indianapolis, Indiana, United States, 46202
United States, Missouri
Washington University School of Medicine- Siteman Cancer Center Active, not recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Icahn School of Medicine at Mount Sinai Active, not recruiting
New York, New York, United States, 10128
Sponsors and Collaborators
Georgetown University
Ipsen
Investigators
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Study Chair: Benjamin Weinberg, MD Georgetown University
More Information
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Responsible Party: Georgetown University
ClinicalTrials.gov Identifier: NCT04005339    
Other Study ID Numbers: 2018-0877
First Posted: July 2, 2019    Key Record Dates
Last Update Posted: December 22, 2023
Last Verified: December 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Georgetown University:
Advanced Biliary Tract Cancer
Biliary Tract Cancer
GI Cancer
Biliary Cancer
NAPOLI-2
Additional relevant MeSH terms:
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Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Leucovorin
Fluorouracil
Irinotecan
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
 Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients