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

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.

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