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

Primary Purpose

Stage IA Pancreatic Cancer, Stage IB Pancreatic Cancer, Stage IIA Pancreatic Cancer

Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
metformin hydrochloride
pharmacological study
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage IA Pancreatic Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    No Intervention

    Experimental

    Experimental

    Arm Label

    Group I (observation)

    Group II (metformin hydrochloride)

    Group III (metformin hydrochloride)

    Arm Description

    Patients undergo observation.

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

    Patients receive metformin hydrochloride as in Group II.

    Outcomes

    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
    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)
    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
    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
    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.

    Full Information

    First Posted
    September 27, 2013
    Last Updated
    July 14, 2015
    Sponsor
    Case Comprehensive Cancer Center
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01954732
    Brief Title
    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

    2. Study Status

    Record Verification Date
    July 2015
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Slow accrual
    Study Start Date
    January 2014 (undefined)
    Primary Completion Date
    March 2015 (Actual)
    Study Completion Date
    March 2015 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Case Comprehensive Cancer Center
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. 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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Stage IA Pancreatic Cancer, Stage IB Pancreatic Cancer, Stage IIA Pancreatic Cancer, Stage IIB Pancreatic Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Group I (observation)
    Arm Type
    No Intervention
    Arm Description
    Patients undergo observation.
    Arm Title
    Group II (metformin hydrochloride)
    Arm Type
    Experimental
    Arm Description
    Patients receive metformin hydrochloride PO BID for at least 7 days in the absence of disease progression or unacceptable toxicity.
    Arm Title
    Group III (metformin hydrochloride)
    Arm Type
    Experimental
    Arm Description
    Patients receive metformin hydrochloride as in Group II.
    Intervention Type
    Drug
    Intervention Name(s)
    metformin hydrochloride
    Other Intervention Name(s)
    Glucophage
    Intervention Description
    Given PO
    Intervention Type
    Other
    Intervention Name(s)
    pharmacological study
    Other Intervention Name(s)
    pharmacological studies
    Intervention Description
    Correlative studies
    Primary Outcome Measure Information:
    Title
    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
    Description
    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.
    Time Frame
    At time of surgery (after 7 days of treatment)
    Secondary Outcome Measure Information:
    Title
    Occurrence of grade 3 and 4 toxicities according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE; version 4.0)
    Description
    Will be summarized as the percentage of patients by type and grade according to treatment group.
    Time Frame
    Baseline to 30 days after treatment has been discontinued or after the date of surgery, whichever occurs first
    Title
    Expression of pACC and pMTOR quantified by the mean fluorescence intensity (MFI) in tissue samples
    Description
    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.
    Time Frame
    At time of surgery (after 7 days of treatment)
    Title
    Percentage of pancreatic cancer stem cells in tissue samples
    Description
    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.
    Time Frame
    At time of surgery (after 7 days of treatment)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Jennifer Eads, MD
    Organizational Affiliation
    Case Comprehensive Cancer Center
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

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

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