A Trial of Systemic Chemotherapy in Combination With Conventional Transarterial Chemoembolization in Patients With Advanced Intra-Hepatic Cholangiocarcinoma

NCT ID: NCT02994251

Last Updated: 2019-12-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-21
• Study Completion Date: 2018-11-06

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.

Conditions

Unresectable Intrahepatic Cholangiocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

gemcitabine

Intervention Type: DRUG

1000 mg/m\^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities

Cisplatin

Intervention Type: DRUG

25 mg/m\^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities

Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C

Intervention Type: DRUG

If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand.

Interventions

gemcitabine

1000 mg/m\^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities

Intervention Type: DRUG

Cisplatin

25 mg/m\^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities

Intervention Type: DRUG

Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C

If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand.

Intervention Type: DRUG

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 B7.
• 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
• Total bilirubin ≤ 2.5 mg/dL
• Platelets ≥ 100,000/mm3
• For TACE procedures, subjects are allowed to have platelets ≥ 75,000/mm3.
• Disease is liver-dominant with >70% of measurable disease burden within the hepatic parenchyma.
• No prior surgery or chemotherapy for ICC.
• ECOG performance status of 0-1.
• No other active malignancy within 2 years.
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of the study.
• Ability to understand and willingness to sign a written informed consent document.

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.
• Current, recent (within 4 weeks of first infusion of this study), or planned participation in additional experimental drug.
• Unstable angina.
• New York Heart Association (NYHA) Grade II or greater congestive heart failure (Appendix C).
• History of myocardial infarction or CVA within 6 months prior to study enrollment.
• Clinically significant peripheral vascular disease.
• Inability to comply with study and/or follow-up procedures.
• Life expectancy of less than 12 weeks.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Todd Schlachter

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Smilow Cancer Center

New Haven, Connecticut, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1603017367

Identifier Type: -

Identifier Source: org_study_id