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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01954732
Recruitment Status : Withdrawn (Slow accrual)
First Posted : October 7, 2013
Last Update Posted : July 15, 2015
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Stage IA Pancreatic Cancer Stage IB Pancreatic Cancer Stage IIA Pancreatic Cancer Stage IIB Pancreatic Cancer Drug: metformin hydrochloride Other: pharmacological study Phase 1

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 Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pharmacodynamic Study of Metformin in Patients With Resectable Pancreatic Cancer
Study Start Date : January 2014
Primary Completion Date : March 2015
Study Completion Date : March 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

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


Outcome Measures

Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01954732


Sponsors and Collaborators
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Jennifer Eads, MD Case Comprehensive Cancer Center
More Information

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01954732     History of Changes
Other Study ID Numbers: CASE1213
NCI-2013-01836 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CASE 1213 ( Other Identifier: Case Comprehensive Cancer Center )
P30CA043703 ( U.S. NIH Grant/Contract )
First Posted: October 7, 2013    Key Record Dates
Last Update Posted: July 15, 2015
Last Verified: July 2015

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs