CPI-613 in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

Phase 1

Completed

• Conditions: Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer
• Interventions: Drug: 6,8-bis(benzylthio)octanoic acid

• Registration Number: NCT01839981
• Lead Sponsor: Wake Forest University Health Sciences

Brief Summary

This pilot clinical trial studies 6,8-bis(benzylthio)octanoic acid in treating patients with locally advanced or metastatic pancreatic cancer. Drugs used in chemotherapy, such as 6,8-bis(benzylthio)octanoic acid, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine initial estimates of overall survival (OS).

SECONDARY OBJECTIVES:

I. To determine response rate. II. To determine progression free survival (PFS).

OUTLINE:

Patients receive 6,8-bis(benzylthio)octanoic acid intravenously (IV) over 2 hours on days 1-5 of week 1 (pre-course 1 only), days 1 and 4 of weeks 2 and 3 (course 1 only), and days 1 and 4 of weeks 1-3 (courses 2-6). Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2013-04-23
• Study First Submitted QC: 2013-04-24
• Study First Posted: 2013-04-25
• Study Start: 2013-07
• Primary Completion: 2015-10
• Study Completion: 2015-10
• Status Verified: 2018-06
• Last Update Submitted: 2018-12-26
• Last Update Posted: 2018-12-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Histologically and cytologically proven locally advanced or metastatic pancreatic adenocarcinoma that is not amenable to surgery, radiation, or combined modality therapy with curative intent, and has failed or is not eligible for available chemotherapies
• 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 of 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 one 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 (=< 5x UNL if liver metastases present)
• Bilirubin =< 1.5 x UNL
• Serum creatinine =< 2.0 mg/dL or 177 umol/L
• International normalized ratio (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

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Exclusion Criteria

• Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication within the past two weeks prior to initiation of CPI-613 (6,8-bis(benzylthio)octanoic acid) 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
• 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 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, 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 < 45%
• 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (6,8-bis(benzylthio)octanoic acid)	6,8-bis(benzylthio)octanoic acid	Patients receive 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-5 of week 1 (pre-course 1 only), days 1 and 4 of weeks 2 and 3 (course 1 only), and days 1 and 4 of weeks 1-3 (courses 2-6). Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Overall Survival	From the first dose of 6,8-bis(benzylthio)octanoic acid to death, assessed up to 3 years	Survival curves for OS will be estimated using Kaplan-Meier techniques.

Secondary Outcome Measures

Name	Time	Method
Safety profile assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0	Up to 3 years
Response rate	Up to 3 years	The proportion of patients who are complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be presented. The proportion of responders will be estimated as the percent of patients who are CR or PR. A 95% confidence interval will be included.
Progression Free Survival	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	Survival curves for PFS will be estimated using Kaplan-Meier techniques.

Trial Locations

Locations (1)

Comprehensive Cancer Center of Wake Forest University; 🇺🇸 Winston-Salem, North Carolina, United States