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

NCT02994251 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 1603017367
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Unresectable Intrahepatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  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.

  12 months

Secondary Outcomes (6)

• Overall Survival

  18 months

• Overall Time to Progression (TTP)

  up to 18 months

• Time to Untreatable Progression (TTUP)

  up to 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 Progression Free Survival

  18 months

Study Arms (1)

All subjects

EXPERIMENTAL

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.

Drug: gemcitabine; Drug: Cisplatin; Drug: Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C

Interventions

gemcitabine DRUG

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

All subjects

Cisplatin DRUG

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

All subjects

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

All subjects

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Smilow Cancer Center

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Interventions

Gemcitabine; Cisplatin; Mitomycin

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Trial was terminated early due to low enrollment, leading to endpoints not being achievable.

Results Point of Contact

• Title: Dr. Todd Schlachter
• Organization: Yale University

todd.schlachter@yale.edu

203-785-5885

Study Officials

• Todd Schlachter

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2016
• First Posted: December 15, 2016
• Study Start: June 21, 2017
• Primary Completion: November 6, 2018
• Study Completion: November 6, 2018
• Last Updated: December 30, 2019
• Results First Posted: December 30, 2019

Record last verified: 2019-12

Locations

US (1)