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

Advanced Biliary Tract Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04005339
• Other study ID #: 2018-0877
• Status: Recruiting
• Phase: Phase 2
• Start date: July 29, 2019
• Est. completion date: July 31, 2024

Study information

• Verified date: December 2023
• Source: Georgetown University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: July 31, 2024
• Est. primary completion date: May 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Biliary Tract Cancer
• Biliary Tract Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Indiana University Health Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Washington University School of Medicine- Siteman Cancer Center	Saint Louis	Missouri
United States	Lombardi Comprehensive Cancer Center, Georgetown University	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Georgetown University	Ipsen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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