A Phase II Trial of Systemic Chemotherapy (Gemcitabine and Cisplatin) in Combination With Conventional Transarterial Chemoembolization (cTACE) in Patients With Advanced Intra-Hepatic Cholangiocarcinoma (ICC)
Overview
- Phase
- Phase 2
- Intervention
- gemcitabine
- Conditions
- Unresectable Intrahepatic Cholangiocarcinoma
- Sponsor
- Yale University
- Enrollment
- 1
- Locations
- 1
- Primary Endpoint
- Progression-free Survival
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
Brief Summary
The study will be a single-center, single-arm, Phase II study of gemcitabine and cisplatin in combination with conventional trans-arterial chemoembolization therapy in adult patients with advanced ICC. 25 patients will be enrolled over the course of 2 years, with an additional 1.5 years for patient follow-up.
Detailed Description
Eligible patients enrolled on study will receive a chemotherapy regimen of gemcitabine and cisplatin administered intravenously on Days 1 and 8 of a 21-day cycle. After every 2 cycles of systemic chemotherapy, patients will receive contrast-enhanced MRI to assess liver disease; conventional trans-arterial chemoembolization (TACE) will be performed as indicated based on this assessment. Patients will receive a maximum of 8 cycles of the gemcitabine/cisplatin combination. Up to 3 TACE treatments may be delivered in this same time frame, with the first TACE taking place after 2 cycles of systemic chemotherapy. Following the treatment period, patients will continue clinical follow-up at 3 month intervals until study exit at 18 months post the start of treatment. It is hypothesized that the addition of conventional transarterial chemoembolization to standard chemotherapy will result in an improvement in PFS in patients with advanced, unresectable ICC, including patients with extra-hepatic disease.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient is at least 18 years of age.
- •Patient has advanced, unresectable intrahepatic cholangiocarcinoma (ICC). Advanced, unresectable ICC is defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection.
- •Eligible for conventional TACE as defined by local treatment guidelines.
- •Child-Pugh class of A to B
- •Adequate end-organ and bone marrow function as manifested as:
- •Hemoglobin ≥ 9 g/dL
- •Absolute neutrophil count ≥ 1500/mm3
- •Creatinine ≤ 2.0 g/dL
- •AST and ALT ≤ 5 x ULN
- •Albumin ≥ 2.4 mg/dL
Exclusion Criteria
- •Prior or concurrent chemotherapy treatment for advanced ICC.
- •History of allergic reactions attributed to compounds of similar chemical or biological composition to gemcitabine, cisplatin, doxorubicin, or mitomycin-C.
- •Active treatment with CYP3A4 strong inhibitors or inducers.
- •Recent surgical procedure within 21 days of study enrollment.
- •Severe and/or uncontrolled co-morbid medical conditions including, but not limited to, active infection, viral hepatitis, congestive heart failure, cardiac arrhythmia, unstable angina pectoris, and psychiatric illness or social circumstance that would limit compliance with study requirements.
- •Pregnancy during study duration.
- •Active immunosuppressive medications.
- •Presence of grade 2 or higher hepatic encephalopathy.
- •Complete occlusion of the entire portal venous system. Partial or branch portal vein occlusion allowed if without reversal of flow.
- •Radiotherapy within 21 days from treatment with study interventions or medications.
Arms & Interventions
All subjects
Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection.
Intervention: gemcitabine
All subjects
Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection.
Intervention: Cisplatin
All subjects
Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection.
Intervention: Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C
Outcomes
Primary Outcomes
Progression-free Survival
Time Frame: 12 months
The primary objective of this study is to evaluate the 12-month progression-free survival (PFS) rate in adult patients with intrahepatic cholangiocarcinoma (ICC) after treatment with gemcitabine and cisplatin in combination with conventional TACE. This is the percentage of patients alive and free of progression at 12-months from enrollment on study. Radiographic assessment of disease burden will be evaluated by mRECIST and qEASL using an MRI scan obtained at the IR clinic visit.
Secondary Outcomes
- Correlation Between Changes in Dynamic Contrast-enhanced MRI of Liver Lesions and Progression Free Survival(18 months)
- Overall Time to Progression (TTP)(up to 18 months)
- Time to Untreatable Progression (TTUP)(up to 18 months)
- Overall Survival(18 months)
- Toxicities of the Gemcitabine and Cisplatin Regimen in Combination With cTACE Therapy Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.(18 months)
- Correlation Between Changes in Dynamic Contrast-enhanced MRI of Liver Lesions and Overall Survival(18 months)