Ricolinostat, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients With Unresectable or Metastatic Cholangiocarcinoma

Unresectable Extrahepatic Bile Duct Carcinoma Clinical Trial

Official title: A Phase Ib, Open-Label, Dose- Escalation Trial of ACY-1215 in Combination With Gemcitabine and Cisplatin in Patients With Unresectable or Metastatic Cholangiocarcinoma

Status Withdrawn

Clinical Trial Summary

This phase Ib trial studies the side effects and best dose of ricolinostat when given together with gemcitabine hydrochloride and cisplatin in treating patients with cholangiocarcinoma that cannot be removed by surgery or has spread to other places in the body. Ricolinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ricolinostat together with gemcitabine hydrochloride and cisplatin may work better in treating patients with cholangiocarcinoma that cannot be removed by surgery or has spread to other places.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) or a dose up to 240 mg/day, whichever is lower, of ricolinostat (ACY-1215) in combination with gemcitabine and cisplatin in patients with unresectable or metastatic cholangiocarcinoma. (Cohort I)

SECONDARY OBJECTIVES:

I. Characterize the safety profile of ACY-1215 in combination with gemcitabine and cisplatin in patients with unresectable or metastatic cholangiocarcinoma. (Both cohorts) II. Determine the single- and multiple-dose pharmacokinetic (PK) of ACY-1215 in combination with gemcitabine and cisplatin in patients with unresectable or metastatic cholangiocarcinoma. (Both cohorts) III. To evaluate tumor response to treatment with ACY-1215 in combination with gemcitabine and cisplatin (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria). (Both cohorts) IV. To assess progression-free and overall survival of patients treated with ACY-1215 in combination with gemcitabine and cisplatin. (Both cohorts)

TERTIARY OBJECTIVES:

I. Both blood and tissue samples will be obtained at baseline and post-treatment cycle 2 for future biomarker development, analysis, and potential blood based molecular/genomic profiling. (Both cohorts) II. Studies on Tissue pre-cycle 1 and post-cycle 2 of therapy will include: phospho extracellular signal-regulated kinases (ERK)1/2; hedgehog-signaling pathways (Gli transcription factors); BIM; histones acetylation; acetylation alpha (a)-tubulin; histone deacetylase (HDAC)6 levels; autophagy markers heat shock protein (HSP)90/70; hypoxia-inducible factor 1 (HIF1)alpha; beclin; microtubule-associated proteins 1A/1B light chain 3 (LC3); Ras homolog gene family member B (RhoB).

OUTLINE: This is a dose-escalation study of ricolinostat.

Patients receive cisplatin intravenously (IV) followed by gemcitabine hydrochloride IV on days 1 and 8, and ricolinostat orally (PO) on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 1 year. ;

Related Conditions & MeSH terms

• Bile Duct Neoplasms
• Carcinoma, Ductal
• Cholangiocarcinoma
• Klatskin Tumor
• Non-Resectable Cholangiocarcinoma
• Recurrent Cholangiocarcinoma
• Stage III Extrahepatic Bile Duct Cancer
• Stage III Intrahepatic Cholangiocarcinoma
• Stage IIIA Hilar Cholangiocarcinoma
• Stage IIIB Hilar Cholangiocarcinoma
• Stage IVA Extrahepatic Bile Duct Cancer
• Stage IVA Hilar Cholangiocarcinoma
• Stage IVA Intrahepatic Cholangiocarcinoma
• Stage IVB Extrahepatic Bile Duct Cancer
• Stage IVB Hilar Cholangiocarcinoma
• Stage IVB Intrahepatic Cholangiocarcinoma
• Unresectable Extrahepatic Bile Duct Carcinoma

• NCT number: NCT02856568
• Study type: Interventional
• Source: Mayo Clinic
• Status: Withdrawn
• Phase: Phase 1
• Start date: May 1, 2017
• Completion date: October 2021