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Trial record 2 of 97 for:    cholangiocarcinoma | Open Studies | Exclude Unknown | "Cholangiocarcinoma"

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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2016 by Mayo Clinic
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT02856568
First received: July 14, 2016
Last updated: August 2, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
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
Drug: Cisplatin
Drug: Gemcitabine Hydrochloride
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Drug: Ricolinostat
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215 [ Time Frame: Cycle 1, Day 1 pre-dose ] [ Designated as safety issue: Yes ]
    PK blood sample

  • MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215 [ Time Frame: Cycle 1, Day 8 pre-dose ] [ Designated as safety issue: Yes ]
    PK blood sample

  • MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215 [ Time Frame: 0.5 hr after ACY-1215 dosing ] [ Designated as safety issue: Yes ]
    PK blood sample

  • MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215 [ Time Frame: 24 hr after Cycle 1, Day 1 only ] [ Designated as safety issue: Yes ]
    PK blood sample

  • MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215 [ Time Frame: Prior to Cycle 1, Day 2 ACY-1215 dosing ] [ Designated as safety issue: Yes ]
    PK blood sample

  • MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215 [ Time Frame: 1 hr after ACY-1215 dosing ] [ Designated as safety issue: Yes ]
    PK blood sample

  • MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215 [ Time Frame: 2hr after ACY-1215 dosing ] [ Designated as safety issue: Yes ]
    PK blood sample

  • MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215 [ Time Frame: 4 hr after ACY-1215 dosing ] [ Designated as safety issue: Yes ]
    PK blood sample

  • MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215 [ Time Frame: 6-8 hr after ACY-1215 dosing ] [ Designated as safety issue: Yes ]
    PK blood sample


Secondary Outcome Measures:
  • Best Response defined as the best objective status recorded using RECIST version 1.1 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Responses will be summarized by simple descriptive summary statistics.

  • 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 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    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.

  • Incidence of adverse events evaluated via the ordinal common toxicity criteria (CTC) toxicity grading of 3+ [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    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.

  • Time to any hematologic nadirs (ANC, platelets, hemoglobin) [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Will be summarized descriptively.

  • Time to any treatment related grade 3+ toxicity [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Will be summarized descriptively.

  • Time to any treatment related toxicity [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Will be summarized descriptively.

  • Time to progression [ Time Frame: From registration to documentation of progression, up to 1 year ] [ Designated as safety issue: No ]
    Will be summarized descriptively.

  • Time to treatment failure [ Time Frame: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient assessed up to 1 year ] [ Designated as safety issue: No ]
    Will be summarized descriptively.


Other Outcome Measures:
  • Laboratory correlates measured from tissue by western blot [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    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.

  • Laboratory correlates measured from tissue by immunofluorescence [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 47
Study Start Date: October 2016
Estimated Primary Completion Date: October 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cisplatin, gemcitabine hydrochloride, ricolinostat)
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
Given IV
Other Names:
  • 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
Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Drug: Ricolinostat
Given PO
Other Names:
  • ACY-1215
  • Histone Deacetylase 6 InhibitorACY-1215

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Prior embolization, chemoembolization, or radiofrequency ablation permitted if >= 4 weeks from registration and evidence of new tumor growth is present

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02856568

Locations
United States, Arizona
Mayo Clinic in Arizona Not yet recruiting
Scottsdale, Arizona, United States, 85259
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Mitesh J. Borad         
United States, Florida
Mayo Clinic in Florida Not yet recruiting
Jacksonville, Florida, United States, 32224-9980
Contact: Clinical Trials Referral Office    855-776-0015    Mody.Kabir@mayo.edu   
Principal Investigator: Kabir Mody         
United States, Minnesota
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Steven R. Alberts         
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
Principal Investigator: Kabir Mody Mayo Clinic in Florida
  More Information

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT02856568     History of Changes
Other Study ID Numbers: MC1542  NCI-2016-01057  MC1542  P30CA015083 
Study First Received: July 14, 2016
Last Updated: August 2, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cholangiocarcinoma
Bile Duct Neoplasms
Carcinoma, Ductal
Klatskin Tumor
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
Neoplasms, Ductal, Lobular, and Medullary
Gemcitabine
Cisplatin
Succinylcholine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Neuromuscular Depolarizing Agents

ClinicalTrials.gov processed this record on September 23, 2016