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

Stage IV Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01835041
• Other study ID #: IRB00022532
• Secondary ID: NCI-2013-00674P3
• Status: Completed
• Phase: Phase 1
• Start date: April 2013
• Est. completion date: March 16, 2023

Study information

• Verified date: July 2023
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: March 16, 2023
• Est. primary completion date: February 28, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acinar Cell Adenocarcinoma of the Pancreas
• Adenocarcinoma
• Duct Cell Adenocarcinoma of the Pancreas
• Pancreatic Neoplasms
• Recurrent Pancreatic Cancer
• Stage IV Pancreatic Cancer

Intervention

Drug:
• 6,8-bis(benzylthio)octanoic acid
Given IV
• oxaliplatin
Given IV
• leucovorin calcium
Given IV
• irinotecan hydrochloride
Given IV
• fluorouracil
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Comprehensive Cancer Center of Wake Forest University	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Toxicities	For exploratory purposes - Any toxicities greater than Grade 2 or above will be assessed for safety of use of CPI-613 and mFOLFIRINOX.	Approximately 2 month after start of treatment or completion of Cycle 2
Other	Overall Survival	For exploratory purposes - Overall survival curve will be measured using Kaplan-Meier methods. Medial survival rates will be examined using a 95% confidence interval.	Approximately 6 months after start of treatment
Other	Progression-Free Survival	For exploratory purposes - The duration of clinical response (evaluated by progression free survival) will be measured from the date a first objective response is documented until the first sign of progression assessed by MRI.	Approximately 2 months after start of treatment
Other	Number of Participants with a Clinical Response	For exploratory purposes - CA-19-9 will be collected every fourth cycle along with MRI of the abdomen and contrast CT of the chest for clinical response.	Approximately 2 months after start of treatment
Primary	Maximum Tolerated Dose	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	2 weeks