Neoplasms

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Rare Diseases

Carcinoma

Recurrence

Cholangiocarcinoma

Klatskin Tumor

Carcinoma, Ductal

Bile Duct Neoplasms

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Bile Duct Diseases

Biliary Tract Diseases

Gastrointestinal Diseases

Bile Duct Cancer

Intrahepatic Cholangiocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Cisplatin

Ricolinostat

Antimetabolites

Histone Deacetylase Inhibitors

Enzyme Inhibitors

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

Gemcitabine Hydrochloride

Laboratory Biomarker Analysis

Pharmacological Study

Kabir Mody

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.

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.

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

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

Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures like response will be carried out in an exploratory manner.

Responses will be summarized by simple descriptive summary statistics.

Will be evaluated using all cycles of treatment. Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group). The number of responses may indicate further evaluation for specific tumor types in a Phase II setting.

Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

National Cancer Institute (NCI)

Mayo Clinic

Liver Neoplasms

Hematinics

Liver Extracts

Patients undergo 15 fractions of image-guided radiation therapy delivered over 19-26 or 27-34 days.

Image Guided Radiation Therapy

Theodore Hong

This randomized phase III trial studies how well gemcitabine hydrochloride and cisplatin with or without radiation therapy work in treating patients with localized liver cancer that cannot be removed by surgery. 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. Radiation therapy uses high energy x rays to kill tumor cells. It is not yet known whether giving gemcitabine and cisplatin is more effective with or without radiation therapy in this patient population. Patients register to this study after receiving gemcitabine and cisplatin.

PRIMARY OBJECTIVES:

I. To evaluate the addition of liver-directed radiation therapy with respect to overall survival (OS) for patients with unresectable, localized intrahepatic cholangiocarcinoma.

SECONDARY OBJECTIVES:

I. To evaluate the addition of liver-directed radiation therapy with respect to local control for patients with unresectable, localized intrahepatic cholangiocarcinoma.

II. To evaluate the addition of liver-directed radiation therapy with respect to adverse events for patients with unresectable, localized intrahepatic cholangiocarcinoma.

III. To evaluate the addition of liver-directed radiation therapy with respect to regional control for patients with unresectable, localized intrahepatic cholangiocarcinoma.

IV. To evaluate the addition of liver-directed radiation therapy with respect to distant metastases for patients with unresectable, localized intrahepatic cholangiocarcinoma.

V. To evaluate the addition of liver-directed radiation therapy with respect to progression-free survival for patients with unresectable, localized intrahepatic cholangiocarcinoma.

After completion of study treatment, patients are followed up every 3 months for 3 years then every 6 months for 2 years.

Randomization ratio (Experimental:Observation) = 2:1

Radiation Therapy vs. Observation Following Gemcitabine and Cisplatin for Inoperable Localized Liver Cancer

Randomized Phase III Study of Focal Radiation Therapy for Unresectable, Localized Intrahepatic Cholangiocarcinoma

Overall survival time is defined as time from randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.

NRG Oncology

No adverse event data was collected on this study due to early termination.

Liver-directed radiation therapy

Radiation Therapy: Patients undergo 15 fractions of image-guided radiation therapy delivered over 19-26 or 27-34 days.

Radiation Therapy

Observation

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

This study stopped accrual early due to unmet targeted accrual goals with 1 subject accrued out of 146 planned. The registered subject withdrew consent the same day as randomization and therefore has no outcome data.

Wendy Seiferheld

Overall Survival

Distant Metastases

Incidence of Adverse Events Evaluated Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

Local Progression

Progression-free Survival (PFS)

Regional Progression Defined as Progression or Existing or Appearance of New Nodal Disease

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Ricolinostat, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients With Unresectable or Metastatic Cholangiocarcinoma	NCT02856568	Non-Resectable ... Recurrent Chola... Stage III Extra... Stage III Intra... Stage IIIA Hila... Stage IIIB Hila... Stage IVA Extra... Stage IVA Hilar... Stage IVA Intra... Stage IVB Extra... Stage IVB Hilar... Stage IVB Intra... Unresectable Ex...	Cisplatin Gemcitabine Hyd... Laboratory Biom... Pharmacological... Ricolinostat	18 Years -	Mayo Clinic
Radiation Therapy vs. Observation Following Gemcitabine and Cisplatin for Inoperable Localized Liver Cancer	NCT02200042	Stage III Intra... Stage IVA Intra...	Image Guided Ra...	18 Years -	NRG Oncology

Spots Global Cancer Trial Database for stage iii intrahepatic cholangiocarcinoma