Clinical trial NCT01954732: Metformin Hydrochloride in Treating Patients With Pancreatic Cancer That Can be Removed by Surgery
Official title: A Pharmacodynamic Study of Metformin in Patients With Resectable Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Stage IA Pancreatic Cancer
Stage IB Pancreatic Cancer
Stage IIA Pancreatic Cancer
Stage IIB Pancreatic Cancer
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-10-07
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: 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
timeFrame: At time of surgery (after 7 days of treatment)
Secondary outcomes:
measure: Occurrence of grade 3 and 4 toxicities according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE; version 4.0)
timeFrame: Baseline to 30 days after treatment has been discontinued or after the date of surgery, whichever occurs first
measure: Expression of pACC and pMTOR quantified by the mean fluorescence intensity (MFI) in tissue samples
timeFrame: At time of surgery (after 7 days of treatment)
measure: Percentage of pancreatic cancer stem cells in tissue samples
timeFrame: At time of surgery (after 7 days of treatment)
Other outcomes:
Locations:
Study officials:
affiliation: Case Comprehensive Cancer Center
name: Jennifer Eads, MD
role: PRINCIPAL_INVESTIGATOR
References: