CPI-613 in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
Primary Purpose
Acinar Cell Adenocarcinoma of the Pancreas, Duct Cell Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
6,8-bis(benzylthio)octanoic acid
Sponsored by
About this trial
This is an interventional treatment trial for Acinar Cell Adenocarcinoma of the Pancreas
Eligibility Criteria
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
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
Sites / Locations
- Comprehensive Cancer Center of Wake Forest University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (6,8-bis(benzylthio)octanoic acid)
Arm Description
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.
Outcomes
Primary Outcome Measures
Overall Survival
Survival curves for OS will be estimated using Kaplan-Meier techniques.
Secondary Outcome Measures
Response rate
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
Survival curves for PFS will be estimated using Kaplan-Meier techniques.
Safety profile assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Full Information
NCT ID
NCT01839981
First Posted
April 23, 2013
Last Updated
December 26, 2018
Sponsor
Wake Forest University Health Sciences
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT01839981
Brief Title
CPI-613 in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
Official Title
A Pilot Study: Open-Label Clinical Trial of CPI-613 in Patients With Metastatic Pancreatic Adenocarcinoma and Poor Performance Status
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
July 2013 (undefined)
Primary Completion Date
October 2015 (Actual)
Study Completion Date
October 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acinar Cell Adenocarcinoma of the Pancreas, Duct Cell Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (6,8-bis(benzylthio)octanoic acid)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
6,8-bis(benzylthio)octanoic acid
Other Intervention Name(s)
alpha-lipoic acid analogue CPI-613, CPI-613
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Overall Survival
Description
Survival curves for OS will be estimated using Kaplan-Meier techniques.
Time Frame
From the first dose of 6,8-bis(benzylthio)octanoic acid to death, assessed up to 3 years
Secondary Outcome Measure Information:
Title
Response rate
Description
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.
Time Frame
Up to 3 years
Title
Progression Free Survival
Description
Survival curves for PFS will be estimated using Kaplan-Meier techniques.
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
Title
Safety profile assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame
Up to 3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Caio Rocha Lima, MD
Organizational Affiliation
Wake Forest University Health Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Comprehensive Cancer Center of Wake Forest University
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
12. IPD Sharing Statement
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CPI-613 in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
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