Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Metformin Combined With Gemcitabine as Adjuvant Therapy for Pancreatic Cancer After Curative Resection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02005419
Recruitment Status : Completed
First Posted : December 9, 2013
Last Update Posted : February 5, 2019
Sponsor:
Information provided by (Responsible Party):
Xian-Jun Yu, Fudan University

Brief Summary:
Pancreatic cancer represents the most lethal of the common malignancies with a 5-year survival rate of less than 5%. For patients who are eligible for potentially curative resection, despite mortality and morbidity rates after surgery have improved, the recurrence rate is up to 85% within 2 years. Data from clinical trials indicate that adjuvant chemotherapy enhances 5-year survival to ~25% for patients who have undergone surgery to remove their tumor; and gemcitabine is the standard regimen of chemotherapy. Metformin is the first-line treatment for type 2 diabetes mellitus. Literatures reported that metformin might inhibit tumor growth by blocking some enzymes needed for cell growth. Some retrospective studies have revealed that diabetic patients taking metformin were less likely to develop pancreatic cancer. Additionally, pancreatic cancer patients treated with metformin showed a better survival than those without metformin. In this study, the researchers intend to investigate the activity and safety of the combination of gemcitabine and metformin in treating patients with pancreatic cancer that have removed by surgery.

Condition or disease Intervention/treatment Phase
Stage IA Pancreatic Adenocarcinoma Stage IB Pancreatic Adenocarcinoma Stage IIA Pancreatic Adenocarcinoma Stage IIB Pancreatic Adenocarcinoma Drug: Gemcitabine Drug: Metformin Drug: placebo Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of the Combination of Gemcitabine and Metformin in Treating Patients With Pancreatic Cancer After Curative Resection
Actual Study Start Date : December 2013
Actual Primary Completion Date : February 2017
Actual Study Completion Date : December 2017


Arm Intervention/treatment
Placebo Comparator: gemcitabine + placebo
gemcitabine at 1000 mg/m^2 on days 1, 8, and 15; placebo at 2 g on days 1-28
Drug: Gemcitabine
Patients receive gemcitabine 1000 mg/m^2 (iv, 30 minutes) on days 1, 8, and 15 for 3 weeks, followed by one week without treatment, and also receive placebo (Arm I)/ metformin (Arm II) on days 1-28. Treatment repeats every 4 weeks for up to 6 circles in the absence of disease recurrence or unacceptable toxicity.
Other Name: GEMZAR

Drug: placebo
Placebo will be administered at a dose of 500 mg twice daily. If well tolerated, the dose will be increased to 1000 mg twice daily in the second week. Treatment repeats every 4 weeks (2 g on days 1-28) for up to 6 circles in the absence of disease recurrence or unacceptable toxicity.

Experimental: gemcitabine + metformin
gemcitabine at 1000 mg/m^2 on days 1, 8, and 15; metformin at 2 g on days 1-28
Drug: Gemcitabine
Patients receive gemcitabine 1000 mg/m^2 (iv, 30 minutes) on days 1, 8, and 15 for 3 weeks, followed by one week without treatment, and also receive placebo (Arm I)/ metformin (Arm II) on days 1-28. Treatment repeats every 4 weeks for up to 6 circles in the absence of disease recurrence or unacceptable toxicity.
Other Name: GEMZAR

Drug: Metformin
Metformin will be administered at a dose of 500 mg twice daily. If well tolerated, the dose will be increased to 1000 mg twice daily in the second week. Treatment repeats every 4 weeks (2 g on days 1-28) for up to 6 circles in the absence of disease recurrence or unacceptable toxicity.
Other Name: glucophage




Primary Outcome Measures :
  1. Recurrence-free survival at one year after curative resection [ Time Frame: From date of randomization (after curative resection) until the date of first documented recurrence or date of death from any cause, whichever came first, assessed 2 months during therapy and 3 months thereafter up to 24 months ]
    To evaluate the therapeutic efficacy of gemcitabine chemotherapy with versus without metformin hydrochloride in terms of recurrence-free survival in patients with pancreatic cancer at one year after curative resection. Computed tomography (CT) scan


Secondary Outcome Measures :
  1. Overall survival after curative resection [ Time Frame: From date of randomization (after curative resection) until the date of death from any cause, assessed one month during therapy and 3 months thereafter up to 24 months ]
    To evaluate the overall survival of patients (after curative resection) treated with this regimen. Outpatient visit, phone interview

  2. Quality of life score after curative resection [ Time Frame: One month during therapy and 3 months thereafter up to 24 months ]
    To evaluate the quality of life score of patients (after curative resection) treated with this regimen. Outpatient visit, phone interview

  3. Number of grade 3 and 4 toxicities according to NCI CTCAE version 4.0 [ Time Frame: One week during therapy and 3 months thereafter up to 24 months ]
    To evaluate the occurrence of grade 3 and 4 toxicities according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE; version 4.0) in patients treated with this regimen. The toxicity profile includes but not limits neutropenia, thrombocytopenia, peripheral neuropathy, hypoglycemia, metabolic acidosis (acute or chronic, including ketoacidosis), which will be summarized as the percentage of patients by type and grade according to treatment group. Outpatient visit, laboratory findings



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed content obtained prior to treatment
  • Age ≥ 18 years and ≤ 80 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Patients must have histologically confirmed pancreatic adenocarcinoma (or any mixed pathology if adenocarcinoma is predominant) after curative resection (R0). The pathological staging does not exceed the stage IIB.
  • No tumor lesions are seen by abdominal and thoracic CT scan 4~8 weeks after surgery, and no serious adverse events are occurred during this period
  • The expected survival after surgery ≥ 6 months
  • White blood cell (WBC) ≥ 3 × 10^9/L; Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; Platelets (PLT) ≥ 100 × 10^9/L; Hemoglobin (Hgb) ≥ 9 g/dL
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]/ alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) ≤ 2.5 × institutional upper limit of normal (ULN); Total bilirubin (TBIL) ≤ ULN; Creatinine (CRE) ≤ 1.5 × ULN
  • Prothrombin time (PT) and international normalized ratio (INR) ≤ 1.5 × ULN
  • Patients with diabetes (diagnosed after surgery) are eligible for this trial; all diabetic patients who are enrolled on this study should discuss the need to change their diabetes management regimen with their primary care physician or endocrinologist prior to enrollment
  • Diabetic patients who are on metformin are eligible as long as they have been on metformin for less than 6 months (estimated 6 months or less duration of metformin therapy from start of metformin to enrollment on study)

Exclusion Criteria:

  • Active second primary malignancy or history of second primary malignancy within the last 3 years
  • Patients who have received any form of anti-tumor therapy before surgery, including chemotherapy, radiotherapy, interventional chemoembolization, radiofrequency ablation, and molecular targeted therapy
  • Use of any other investigational agents
  • Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, internal hemorrhage, pancreatic leakage, bile leakage, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • History of allergic reactions attributed to compounds of similar chemical or biological composition to metformin or gemcitabine
  • Current use of metformin for more than 6 months prior to enrollment on study
  • Metabolic acidosis, acute or chronic, including ketoacidosis
  • Pregnant or nursing women
  • Human immunodeficiency virus (HIV)-positive patients
  • Patients who are unwilling or unable to comply with study procedures

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02005419


Locations
Layout table for location information
China
Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University
Shanghai, China, 200032
Sponsors and Collaborators
Xian-Jun Yu
Investigators
Layout table for investigator information
Principal Investigator: Xianjun Yu, M.D., Ph.D. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Shanghai Pancreatic Cancer Institute; Pancreatic Cancer Institute, Fudan University. Shanghai, China.

Layout table for additonal information
Responsible Party: Xian-Jun Yu, M.D., Ph.D., Fudan University
ClinicalTrials.gov Identifier: NCT02005419     History of Changes
Other Study ID Numbers: MET1310128-2
First Posted: December 9, 2013    Key Record Dates
Last Update Posted: February 5, 2019
Last Verified: February 2019

Keywords provided by Xian-Jun Yu, Fudan University:
Pancreatic Cancer
Pancreatic Adenocarcinoma
Metformin
Gemcitabine
Adjuvant Therapy

Additional relevant MeSH terms:
Layout table for MeSH terms
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Metformin
Gemcitabine
Hypoglycemic Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors