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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01766219
Recruitment Status : Completed
First Posted : January 11, 2013
Results First Posted : May 15, 2019
Last Update Posted : May 15, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Wake Forest University Health Sciences

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Non-Randomized
Intervention Model: Sequential 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
Actual Primary Completion Date : April 2018
Actual Study Completion Date : May 18, 2018


Arm Intervention/treatment
Experimental: Arm 1: (6,8-bis[benzylthio]octanoic acid) 2,300 mg/m²

Participants will not be treated with CPI-613 during pre-Cycle 1 and will only be treated with 3 weeks on/1 week off at 2,300 mg/m² as a starting dose. If none of these 3 participants develop a dose-limiting toxicity through Cycle 1, the dose for the 3-weeks-on-1-week-off treatment cycles will be 3,000 mg/m² in all subsequent participants in this trial.

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.

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

Experimental: Arm 2: (6,8-bis[benzylthio]octanoic acid) 1,200/3,00 mg/m²

Participants will received pre-cycle 1 week dose at 1200 mg/m² and dosing will escalate to 3,000 mg/m² for the three weeks on, one week off cycle.

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.

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

Experimental: Arm 3 (6,8-bis[benzylthio]octanoic acid) 600/3,000 mg/m²

Participants will received pre-cycle 1 week dose at 600 mg/m² and dosing will escalate to 3,000 mg/m² for the three weeks on, one week off cycle.

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.

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




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: From the first dose of 6,8-bis(benzylthio)octanoic acid to death, assessed up to 4 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) [ Time Frame: From the start of the treatment until disease progression, assessed up to 4 year ]
    Using the RECIST version 1.1 as defined by patient with 95% confidence interval will be included. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note:the appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study

  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 4 years ]
    Estimated using Kaplan-Meier techniques as well as RECIST 1.1. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note:the appearance of one or more new lesions is also considered progression).

  3. Number of Participants With Adverse Events Using the National Cancer Institute Common Terminology Criteria [ Time Frame: Up to 1 month completion of study treatment, assessed up to 1 year ]
    Adverse events will be captured using the National Cancer Institute Common Terminology Criteria (NCI CTCAE) version 3.0



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01766219


Locations
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United States, North Carolina
Comprehensive Cancer Center of Wake Forest University
Winston-Salem, North Carolina, United States, 27157
Sponsors and Collaborators
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Caio Rocha Lima, MD Wake Forest University Health Sciences
  Study Documents (Full-Text)

Documents provided by Wake Forest University Health Sciences:

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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT01766219    
Other Study ID Numbers: IRB00022533
NCI-2013-00063 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA012197 ( U.S. NIH Grant/Contract )
CCCWFU 59212 ( Other Identifier: Wake Forest University Health Sciences )
First Posted: January 11, 2013    Key Record Dates
Results First Posted: May 15, 2019
Last Update Posted: May 15, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Liver Neoplasms
Cholangiocarcinoma
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