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

Case Comprehensive Cancer Center (Case CCC)

Status and phase: Withdrawn; Phase 1

Conditions: Stage IB Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IA Pancreatic Cancer

Treatments: Drug: metformin hydrochloride; Other: pharmacological study

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01954732

P30CA043703 (U.S. NIH Grant/Contract)

CASE1213

NCI-2013-01836 (Registry Identifier)

CASE 1213 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 3 patient groups

Group I (observation)

No Intervention group

Description:

Patients undergo observation.

Group II (metformin hydrochloride)

Experimental group

Description:

Patients receive metformin hydrochloride PO BID for at least 7 days in the absence of disease progression or unacceptable toxicity.

Treatment:

Other: pharmacological study

Drug: metformin hydrochloride

Group III (metformin hydrochloride)

Experimental group

Description:

Patients receive metformin hydrochloride as in Group II.

Treatment:

Other: pharmacological study

Drug: metformin hydrochloride