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

NCT02856568 | Withdrawn Phase 1 FDA Drug

• 3 other identifiers: MC1542NCI-2016-01057P30CA015083
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (9)

• MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

  PK blood sample

  Cycle 1, Day 1 pre-dose

• MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

  PK blood sample

  Cycle 1, Day 8 pre-dose

• MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

  PK blood sample

  0.5 hr after ACY-1215 dosing

• MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

  PK blood sample

  24 hr after Cycle 1, Day 1 only

• MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

  PK blood sample

  Prior to Cycle 1, Day 2 ACY-1215 dosing

• MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

  PK blood sample

  1 hr after ACY-1215 dosing

• MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

  PK blood sample

  2hr after ACY-1215 dosing

• MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

  PK blood sample

  4 hr after ACY-1215 dosing

• MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

  PK blood sample

  6-8 hr after ACY-1215 dosing

Secondary Outcomes (8)

• Best Response defined as the best objective status recorded using RECIST version 1.1

  Up to 1 year

• Confirmed response is defined to be a stringent complete response, complete response, very good partial response, or partial response noted as the objective status on two consecutive evaluations using RECIST version 1.1

  Up to 1 year

• Incidence of adverse events evaluated via the ordinal common toxicity criteria (CTC) toxicity grading of 3+

  Up to 1 year

• Time to any hematologic nadirs (ANC, platelets, hemoglobin)

  Up to 1 year

• Time to any treatment related grade 3+ toxicity

  Up to 1 year

Other Outcomes (2)

• Laboratory correlates measured from tissue by western blot

  Up to 1 year

• Laboratory correlates measured from tissue by immunofluorescence

  Up to 1 year

Study Arms (1)

Treatment (cisplatin, gemcitabine hydrochloride, ricolinostat)

EXPERIMENTAL

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.

Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Ricolinostat

Interventions

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloramine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Treatment (cisplatin, gemcitabine hydrochloride, ricolinostat)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011, LY188011

Treatment (cisplatin, gemcitabine hydrochloride, ricolinostat)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (cisplatin, gemcitabine hydrochloride, ricolinostat)

Pharmacological Study OTHER

Correlative studies

Treatment (cisplatin, gemcitabine hydrochloride, ricolinostat)

Ricolinostat DRUG

Given PO

Also known as: ACY-1215, Histone Deacetylase 6 InhibitorACY-1215

Treatment (cisplatin, gemcitabine hydrochloride, ricolinostat)

Eligibility Criteria

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

You may qualify if:

• Histological or cytologic confirmation of unresectable or metastatic cholangiocarcinoma (intrahepatic, hilar, extrahepatic bile duct)
• Measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Absolute neutrophil count (ANC) \>= 1200/mm\^3
• Platelet count \>= 100,000/mm\^3
• Total bilirubin \< 1.5 x upper limit of normal (ULN), If patient has known Gilbert's syndrome, direct bilirubin \< 2.0 x ULN
• Aspartate transaminase (AST) =\< 5 x ULN
• Alkaline phosphatase =\< 5 x ULN
• Creatinine =\< 1.5 x ULN
• Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
• Ability to complete a patient medication diary by themselves or with assistance
• Provide informed written consent
• Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• Willingness to provide tissue and blood samples for correlative research purposes
• Life expectancy \>= 3 months

You may not qualify if:

• Any of the following
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Central nervous system (CNS) metastasis; NOTE: history of brain metastasis other than locally treatable lesions (i.e., lesions treatable with surgery or radiosurgery); patients with locally treatable disease may be considered for study if they have completed treatment without evidence of CNS progression for \> 4 weeks after completion of treatment; patients with a history of brain or other CNS metastases not amenable to local therapy will not be eligible
• Prior biologic or immunologic therapy =\< 4 weeks prior to study entry
• Prior systemic chemotherapy for cholangiocarcinoma or gallbladder carcinoma; NOTE: adjuvant chemotherapy is allowed if completed \> 6 months prior to the start of registration
• Prior radiation of cholangiocarcinoma or gallbladder carcinoma; NOTE: adjuvant radiation therapy is allowed if completed \> 6 months prior to the start of registration
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• Other active malignancy =\< 5 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix or breast, or prostatic intraepithelial neoplasm; NOTE: if there is a history or prior malignancy, patient must not be receiving other specific treatment (other than hormonal therapy) for their cancer
• History of myocardial infarction =\< 6 months from registration, or congestive heart failure requiring use of ongoing maintenance therapy for life threatening ventricular arrhythmias

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Cholangiocarcinoma; Bile Duct Neoplasms; Klatskin Tumor

Interventions

Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Gemcitabine; ricolinostat

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Kabir Mody

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2016
• First Posted: August 5, 2016
• Study Start: May 1, 2017
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2021
• Last Updated: May 30, 2017

Record last verified: 2017-05

Locations

US (3)