Metformin Hydrochloride In Treating Patients With Pancreatic Cancer That Can Be Removed By Surgery

Study Overview

Metformin Hydrochloride in Treating Patients With Pancreatic Cancer That Can be Removed by Surgery

This randomized clinical trial studies metformin hydrochloride in treating patients with pancreatic cancer that can be removed by surgery. Metformin hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES: I. To determine the effect of escalating doses of metformin (metformin hydrochloride) given pre-operatively on pancreatic cancer cell proliferation and apoptosis. SECONDARY OBJECTIVES: I. To assess toxicity of escalating doses of metformin given pre-operatively in patients with resectable pancreatic carcinoma. II. To measure the effect of metformin on the expression of phosphorylated acetyl-CoA carboxylase alpha (ACC), phosphorylated mechanistic target of rapamycin (serine/threonine kinase) (mTOR), and pancreatic cancer stem cells. OUTLINE: Patients are randomized to 1 of 3 treatment groups. GROUP I: Patients undergo observation. GROUP II: Patients receive metformin hydrochloride orally (PO) twice daily (BID) for at least 7 days in the absence of disease progression or unacceptable toxicity. GROUP III: Patients receive metformin hydrochloride as in Group II. After completion of study treatment, patients are followed up 30 days.

Stage IA Pancreatic Cancer
Stage IB Pancreatic Cancer
Stage IIA Pancreatic Cancer
Stage IIB Pancreatic Cancer

DRUG: metformin hydrochloride
OTHER: pharmacological study

CASE1213
NCI-2013-01836 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
CASE 1213 (OTHER Identifier) (OTHER: Case Comprehensive Cancer Center)
P30CA043703 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2013-09-27	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2015-07-14
First Submitted that Met QC Criteria 2013-09-27	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2015-07-15
First Posted (ESTIMATED) 2013-10-07	Results First Posted N/A	Last Verified 2015-07

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
NO_INTERVENTION: Group I (observation) Patients undergo observation.
EXPERIMENTAL: Group II (metformin hydrochloride) Patients receive metformin hydrochloride PO BID for at least 7 days in the absence of disease progression or unacceptable toxicity.	DRUG: metformin hydrochloride Given PO OTHER: pharmacological study Correlative studies
EXPERIMENTAL: Group III (metformin hydrochloride) Patients receive metformin hydrochloride as in Group II.	DRUG: metformin hydrochloride Given PO OTHER: pharmacological study Correlative studies

Participant Group/Arm

Intervention/Treatment

NO_INTERVENTION: Group I (observation)

Patients undergo observation.

EXPERIMENTAL: Group II (metformin hydrochloride)

Patients receive metformin hydrochloride PO BID for at least 7 days in the absence of disease progression or unacceptable toxicity.

DRUG: metformin hydrochloride

Given PO

OTHER: pharmacological study

Correlative studies

EXPERIMENTAL: Group III (metformin hydrochloride)

Patients receive metformin hydrochloride as in Group II.

DRUG: metformin hydrochloride

Given PO

OTHER: pharmacological study

Correlative studies

Primary Outcome Measures	Measure Description	Time Frame
Pancreatic tumor cell proliferation and apoptosis as measured by the percentage of cells Ki-67+, percentage of cells TUNEL+, and mitotic counts in tissue samples	The difference between treatment groups will be compared using analysis of variance (ANOVA) (3 groups) followed by Tukey's pair-wise comparison procedure. Transformation may be applied (e.g. natural log) prior to analysis to better approximate normality.	At time of surgery (after 7 days of treatment)

Secondary Outcome Measures	Measure Description	Time Frame
Occurrence of grade 3 and 4 toxicities according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE; version 4.0)	Will be summarized as the percentage of patients by type and grade according to treatment group.	Baseline to 30 days after treatment has been discontinued or after the date of surgery, whichever occurs first
Expression of pACC and pMTOR quantified by the mean fluorescence intensity (MFI) in tissue samples	The difference between treatment groups will be compared using ANOVA followed by Tukey's pair-wise comparison procedure. Laser scanning cytometry and iCyte software used to quantify the MFI of pACC and pMTOR.	At time of surgery (after 7 days of treatment)
Percentage of pancreatic cancer stem cells in tissue samples	For each of biologic biomarkers (pACC, pMTOR, CD44+CD24+ESA+ cells), the difference between treatment groups will be compared using ANOVA (3 groups) followed by Tukey's pair-wise comparison procedure. Transformation may be applied (e.g. natural log) prior to analysis to better approximate normality.	At time of surgery (after 7 days of treatment)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Patients must have histologically or cytologically confirmed resectable pancreatic carcinoma; patients with pancreatic neuroendocrine tumors are not eligible
Patients must be previously untreated with chemotherapy or radiation therapy
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Patients must have surgical resection of the pancreas planned, with enrollment at least 7 days prior to surgery; patients with surgery scheduled > 15 days will not be excluded
Hemoglobin (Hg)A1C must be below 7%
Total bilirubin less than 1.5 X institutional upper limit of normal
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X institutional upper limit of normal
Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
Serum creatinine within normal institutional limits
Alkaline phosphatase < 1.5 X institutional upper limit of normal
Subjects must have the ability to understand and be willing to provide written informed consent

History of metformin use in the previous 3 months
Treatment with neoadjuvant chemotherapy or radiation therapy
History of allergic reactions attributed to metformin
Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Metabolic acidosis, acute or chronic, including ketoacidosis
Metastatic disease

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Jennifer Eads, MD, Case Comprehensive Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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Clinical Trial Record