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

July 14, 2015 updated by: Case Comprehensive Cancer Center

A Pharmacodynamic Study of Metformin in Patients With Resectable Pancreatic Cancer

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Phase

  • Phase 1

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

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

How is the study designed?

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.
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Drug: metformin hydrochloride
Given PO
Other Names:
  • Glucophage
Experimental: Group III (metformin hydrochloride)
Patients receive metformin hydrochloride as in Group II.
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Drug: metformin hydrochloride
Given PO
Other Names:
  • Glucophage

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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
Time Frame: At time of surgery (after 7 days of treatment)
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

Outcome Measure
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)
Time Frame: Baseline to 30 days after treatment has been discontinued or after the date of surgery, whichever occurs first
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
Time Frame: At time of surgery (after 7 days of treatment)
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
Time Frame: At time of surgery (after 7 days of treatment)
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)

Collaborators and Investigators

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

Sponsor

Case Comprehensive Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Jennifer Eads, MD, Case Comprehensive Cancer Center

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 Major Dates

Study Start

January 1, 2014

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

March 1, 2015

Study Registration Dates

First Submitted

September 27, 2013

First Submitted That Met QC Criteria

September 27, 2013

First Posted (Estimate)

October 7, 2013

Study Record Updates

Last Update Posted (Estimate)

July 15, 2015

Last Update Submitted That Met QC Criteria

July 14, 2015

Last Verified

July 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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