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

Study Overview
=================
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.

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

Conditions
-----------------
Advanced Biliary Tract Cancer

Intervention / Treatment
-----------------
* Drug: Nanoliposomal Irinotecan
* Drug: Leucovorin
* Drug: Fluorouracil


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br>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<br>* Nanoliposomal irinotecan 70 mg/ IV over 90 minutes, every 14 days<br>Drug: Leucovorin<br>* Leucovorin 400 mg/ IV over 30 minutes, every 14 days.<br>Drug: Fluorouracil<br>* Fluorouracil 2,400 mg/m IV over 46 hours.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Advanced Biliary Tract Cancer, Biliary Tract Cancer, GI Cancer, Biliary Cancer, NAPOLI-2