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

• Sponsor: Georgetown University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04005339
• Collaborator: Ipsen (Industry)
• Enrollment: 44
• Locations: 3
• Arm: 1
• Anticipated Duration (Months): 48.1
• Patients Per Site: 14.7
• Patients Per Site Per Month: 0.3

Study Details

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.

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

• Study Type: Interventional
• Anticipated 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: Jul 29, 2019
• Anticipated Primary Completion Date: Nov 30, 2022
• Anticipated Study Completion Date: Jul 31, 2023

Arms and Interventions

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

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. [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. 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. [6 months]

   Measured in terms of best overall response rate (ORR).

2. 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. [6 months]

   Measured in terms of median progression-free survival (mPFS).

3. 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. [6 months]

   Measured in terms of median overall survival (mOS).

4. 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. [6 months]

   Measured in terms of median time to disease progression (mTTP).

5. 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. [6 months]

   Measured in terms of disease control rate (DCR).

6. 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. [6 months]

   Measured in terms of median duration of disease control (DDC).

7. 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. [6 months]

   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. [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. [6 months]

   Correlation of tumor genetic mutations and protein expression levels with progression-free survival.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Lombardi Comprehensive Cancer Center, Georgetown University	Washington	District of Columbia	United States	20007
2	Indiana University Health Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
3	Washington University School of Medicine- Siteman Cancer Center	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Georgetown University
• Ipsen

Investigators

• Study Chair: Benjamin Weinberg, MD, Georgetown University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Georgetown University
• ClinicalTrials.gov Identifier: NCT04005339
• Other Study ID Numbers: 2018-0877
• First Posted: Jul 2, 2019
• Last Update Posted: Aug 19, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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: Biliary Tract Neoplasms; Leucovorin; Fluorouracil; Irinotecan

Study Results

No Results Posted as of Aug 19, 2022