CPI-613 and Combination Chemotherapy in Treating Patients With Metastatic Pancreatic Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Comprehensive Cancer Center of Wake Forest University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier:
NCT01835041
First received: April 16, 2013
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

This phase I trial studies the side effects and best dose of CPI-613 when given together with combination chemotherapy in treating patients with metastatic pancreatic cancer. Drugs used in chemotherapy, CPI-613, leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.


Condition Intervention Phase
Acinar Cell Adenocarcinoma of the Pancreas
Duct Cell Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage IV Pancreatic Cancer
Drug: 6,8-bis(benzylthio)octanoic acid
Drug: oxaliplatin
Drug: leucovorin calcium
Drug: irinotecan hydrochloride
Drug: fluorouracil
Other: laboratory biomarker analysis
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 I Open-Label Dose-Escalation Clinical Trial of CPI-613 in Combination With Modified FOLFIRINOX in Patients With Metastatic Pancreatic Cancer and Good Performance Status

Resource links provided by NLM:


Further study details as provided by Comprehensive Cancer Center of Wake Forest University:

Primary Outcome Measures:
  • MTD of 6,8-bis(benzylthio)octanoic acid when used in combination with mFOLFIRINOX determined by dose-limiting toxicities graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 15
Study Start Date: April 2013
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (6,8-bis[benzylthio]octanoic acid, mFOLFIRINOX)
Patients receive 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1 and 3. Patients also receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV continuously over 46 hours on day 1. Treatment repeats every 2 weeks for 6 months in the absence of disease progression or unacceptable toxicity.
Drug: 6,8-bis(benzylthio)octanoic acid
Given IV
Other Names:
  • alpha-lipoic acid analogue CPI-613
  • CPI-613
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of CPI-613 (6,8-bis[benzylthio]octanoic acid), when used in combination with modified leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin (mFOLFIRINOX), in patients with metastatic pancreatic cancer.

SECONDARY OBJECTIVES:

I. To assess the safety of CPI-613/mFOLFIRINOX combination in patients with metastatic pancreatic cancer.

II. To collect tissue for future genomic analyses. III. To obtain preliminary data on efficacy of treatment with CPI-613/mFOLFIRINOX.

OUTLINE: This is a dose-escalation study of 6,8-bis(benzylthio)octanoic acid.

Patients receive 6,8-bis(benzylthio)octanoic acid intravenously (IV) over 2 hours on days 1 and 3. Patients also receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV continuously over 46 hours on day 1. Treatment repeats every 2 weeks for 6 months in the absence of disease progression or unacceptable toxicity.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically and cytologically confirmed metastatic pancreatic adenocarcinoma
  • Eastern Cooperative Oncology Group (ECOG) performance status being 0-1
  • Expected survival > 2 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
  • At least 2 weeks must have elapsed from any prior surgery or hormonal therapy
  • 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 oxalic 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 unless on therapeutic blood thinners
  • 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:

  • Endocrine or acinar pancreatic carcinoma
  • Previous radiotherapy for cerebral metastases, central nervous system (CNS) or epidural tumor
  • Prior treatment with any chemotherapy for metastatic disease from pancreatic cancer
  • Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication within the past 4 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 2 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
  • 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
  • Patients with a history of myocardial infarction that is < 3 months prior to registration
  • Evidence of active infection, or serious infection within the past month
  • Patients with known human immunodeficiency virus (HIV) infection
  • Patients who have received immunotherapy of any type within the past 4 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
  • Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of the patient
  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: NCT01835041

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: Angela T. Alistar         
Sponsors and Collaborators
Comprehensive Cancer Center of Wake Forest University
Investigators
Principal Investigator: Angela Alistar Comprehensive Cancer Center of Wake Forest University
  More Information

No publications provided

Responsible Party: Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier: NCT01835041     History of Changes
Other Study ID Numbers: CCCWFU 57112, NCI-2013-00674, P30CA012197
Study First Received: April 16, 2013
Last Updated: July 21, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma, Acinar Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Oxaliplatin
Irinotecan
Fluorouracil
Camptothecin
Levoleucovorin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents

ClinicalTrials.gov processed this record on October 16, 2014