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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Case Comprehensive Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01954732
First received: September 27, 2013
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pharmacodynamic Study of Metformin in Patients With Resectable Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: Yes ]
    Will be summarized as the percentage of patients by type and grade according to treatment group.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Percentage of pancreatic cancer stem cells in tissue samples [ Time Frame: At time of surgery (after 7 days of treatment) ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 39
Study Start Date: January 2014
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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: NCT01954732

Locations
United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44106-5065
Contact: Neal J. Meropol, MD    216-844-5220    Neal.Meropol@uhhospitals.org   
Principal Investigator: Neal J. Meropol         
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44195
Contact: Bassam N. Estfan, MD    216-445-9449    Estfanb@ccf.org   
Principal Investigator: Bassam N. Estfan         
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Neal Meropol, MD Case Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01954732     History of Changes
Other Study ID Numbers: CASE1213, NCI-2013-01836, CASE 1213, P30CA043703
Study First Received: September 27, 2013
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration

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
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014