CPI-613 in Treating Patients With Advanced or Metastatic Bile Duct Cancer That Cannot Be Removed By Surgery

Study Description

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Brief Summary:

This pilot clinical trial studies 6,8-bis(benzylthio)octanoic acid in treating patients with advanced or metastatic cholangiocarcinoma that cannot be removed by surgery. 6,8-Bis(benzylthio)octanoic acid may stop the growth of cholangiocarcinoma by blocking blood flow to the tumor

Condition or disease	Intervention/treatment	Phase
Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Unresectable Extrahepatic Bile Duct Cancer	Drug: 6,8-bis(benzylthio)octanoic acid	Phase 1; Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the safety and efficacy of CPI-613 (6,8-bis[benzylthio]octanoic acid) in patients with advanced unresectable cholangiocarcinoma who have failed available therapies.

OUTLINE:

Pre-cycle: Patients receive 6,8-bis(benzylthio)octanoic acid intravenously (IV) over 2 hours on days 1-5, 1 week prior to course 1.

Patients receive 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1 and 4 of weeks 1-3. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients responding to treatment may receive up to 4 more courses of treatment.

After completion of study treatment, patients are followed up bimonthly.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	13 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Pilot Open-Label Clinical Trial of CPI-613 in Patients With Advanced Bile Duct Cancers
Study Start Date :	May 2013
Estimated Primary Completion Date :	August 2018
Estimated Study Completion Date :	August 2018

Arms and Interventions

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Arm

Intervention/treatment

Experimental: Treatment (6,8-bis[benzylthio]octanoic acid); Pre-cycle: Patients receive 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-5, 1 week prior to course 1. Patients receive 6,8-bis(benzylthio)octanoic acid IVover 2 hours on days 1 and 4 of weeks 1-3. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients responding to treatment may receive up to 4 more courses of treatment.

Drug: 6,8-bis(benzylthio)octanoic acid; Given IV; Other Names: alpha-lipoic acid analogue CPI-613; CPI-613

Outcome Measures

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Primary Outcome Measures :

1. Overall survival [ Time Frame: From the first dose of 6,8-bis(benzylthio)octanoic acid to death, assessed up to 3 years ]
   Estimated using Kaplan-Meier techniques.

Secondary Outcome Measures :

1. Response rate defined as proportion of patients with complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), using based on the RECIST version 1.1 [ Time Frame: From the start of the treatment until DP, assessed up to 3 year ]
   95% confidence interval will be included.
2. Progression-free survival [ Time Frame: From the first dose of 6,8-bis(benzylthio)octanoic acid to disease progression (DP) or death due to any cause, assessed up to 3 years ]
   Estimated using Kaplan-Meier techniques.
3. Adverse events, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 [ Time Frame: Up to 1 month after completion of study treatment ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Histologically and cytologically proven cholangiocarcinoma of any type (including intrahepatic cholangiocarcinoma, extrahepatic primary cholangiocarcinoma, hilar cholangiocarcinomas, cholangiocarcinomas located in the gall bladder or hepatic capsule effraction, and carcinoma of the Ampulla of Vater, etc.) that is not amenable to surgery, radiation, or combined modality therapy with curative intent, and has failed or is not eligible for available chemotherapies such as gemcitabine with or without platinum
• Local, locally-advanced, or metastatic disease documented as having shown progression on a scan (e.g., computed tomography [CT], magnetic resonance imaging [MRI])
• Measurable tumor according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria with at least one unidimensionally measurable target lesion
• No evidence of biliary duct obstruction, unless obstruction is controlled by local treatment or, in whom the biliary tree can be decompressed by endoscopic or percutaneous stenting with subsequent reduction in bilirubin to below 1.5 x upper level of normal (ULN)
• No acute toxic effects from previous treatment superior to grade 1 at the start of the study
• Eastern Cooperative Oncology Group (ECOG) performance status being 0-3
• Expected survival > 3 months
• Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device) during the study, and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation
• Fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists
• Granulocyte count >= 1500/mm^3
• White blood cell (WBC) >= 3500 cells/mm^3 or >= 3.5 bil/L
• Platelet count >=100,000 cells/mm^3 or >=100 bil/L
• Absolute neutrophil count (ANC) >=1500 cells/mm^3 or >=1.5 bil/L
• Hemoglobin >= 9 g/dL or >= 90 g/L
• Aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase [SGOT]) =< 3 x upper normal limit (UNL), alanine aminotransferase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 3 x UNL (=< 5 x UNL if liver metastases present)
• Bilirubin =< 1.5 x UNL
• Serum creatinine =< 2.0 mg/dL or 177 µmol/L
• International normalized ratio or INR must be =< 1.5
• No evidence of active infection and no serious infection within the past month
• Mentally competent, ability to understand and willingness to sign the informed consent form

Exclusion Criteria:

• Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication within the past 2 weeks prior to initiation of CPI-613 treatment
• Serious medical illness that would potentially increase patients' risk for toxicity
• Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
• Pregnant women, or women of child-bearing potential not using reliable means of contraception (because the teratogenic potential of CPI-613 is unknown)
• Lactating females
• Fertile men unwilling to practice contraceptive methods during the study period
• Life expectancy less than 3 months
• Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients
• Unwilling or unable to follow protocol requirements
• Dyspnea with moderate exertion; patients with clinically significant pleural or pericardial effusions
• Active heart disease including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, symptomatic myocardial infarction, or symptomatic congestive heart failure; also patients with a history of myocardial infarction that is < 1 year prior to registration, or patients with previous congestive heart failure (< 1 year prior to registration) requiring pharmacologic support or with left ventricular ejection fraction < 50%)
• A history of additional risk factors for torsade de pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome)
• Evidence of active infection, or serious infection within the past month
• Patients with known human immunodeficiency virus (HIV) infection
• Patients who have received cancer immunotherapy of any type within the past 2 weeks prior to initiation of CPI-613 treatment
• Requirement for immediate palliative treatment of any kind including surgery
• Patients that have received a chemotherapy regimen with stem cell support in the previous 6 months
• Prior illicit drug addiction
• Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of the patient

Contacts and Locations

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Locations

United States, North Carolina
Comprehensive Cancer Center of Wake Forest University	Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Amy Neal, RN 336-713-6912 aneal@wakehealth.edu
Principal Investigator: Rodwiges Desnoyers

Sponsors and Collaborators

Wake Forest University Health Sciences

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Rodwige Desnoyers	Wake Forest University Health Sciences

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Wake Forest University Health Sciences
ClinicalTrials.gov Identifier:	NCT01766219 History of Changes
Other Study ID Numbers:	CCCWFU 59212; NCI-2013-00063 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); P30CA012197 ( U.S. NIH Grant/Contract )
First Posted:	January 11, 2013
Last Update Posted:	January 26, 2018
Last Verified:	August 2017

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

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