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

Stage IIB Pancreatic Cancer Clinical Trial

Official title:

A Pharmacodynamic Study of Metformin in Patients With Resectable Pancreatic Cancer

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01954732
• Other study ID #: CASE1213
• Secondary ID: NCI-2013-01836CA
• Status: Withdrawn
• Phase: Phase 1
• First received: September 27, 2013
• Last updated: July 14, 2015
• Start date: January 2014
• Est. completion date: March 2015

Study information

• Verified date: July 2015
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Neoplasms
• Stage IA Pancreatic Cancer
• Stage IB Pancreatic Cancer
• Stage IIA Pancreatic Cancer
• Stage IIB Pancreatic Cancer

Intervention

Drug:
• metformin hydrochloride
Given PO

Other:
• pharmacological study
Correlative studies

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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	Yes
Secondary	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)	No
Secondary	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)	No