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

NCT02005419 | Completed Phase 2 DMC

• 1 other identifier: MET1310128-2
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

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.

Conditions

Stage IA Pancreatic Adenocarcinoma; Stage IB Pancreatic Adenocarcinoma; Stage IIA Pancreatic Adenocarcinoma; Stage IIB Pancreatic Adenocarcinoma

Keywords

Pancreatic Cancer; Pancreatic Adenocarcinoma; Metformin; Gemcitabine; Adjuvant Therapy

Outcome Measures

Primary Outcomes (1)

• Recurrence-free survival at one year after curative resection

  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

  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

Secondary Outcomes (3)

• Overall survival after curative resection

  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

• Quality of life score after curative resection

  One month during therapy and 3 months thereafter up to 24 months

• Number of grade 3 and 4 toxicities according to NCI CTCAE version 4.0

  One week during therapy and 3 months thereafter up to 24 months

Study Arms (2)

gemcitabine + placebo

PLACEBO COMPARATOR

gemcitabine at 1000 mg/m\^2 on days 1, 8, and 15; placebo at 2 g on days 1-28

Drug: Gemcitabine; Drug: placebo

gemcitabine + metformin

EXPERIMENTAL

gemcitabine at 1000 mg/m\^2 on days 1, 8, and 15; metformin at 2 g on days 1-28

Drug: Gemcitabine; Drug: Metformin

Interventions

Gemcitabine DRUG

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.

Also known as: GEMZAR

gemcitabine + metformin; gemcitabine + placebo

Metformin DRUG

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.

Also known as: glucophage

gemcitabine + metformin

placebo DRUG

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.

gemcitabine + placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Xian-Jun Yu: lead

Study Sites (1)

Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University

Shanghai, 200032, China

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; Metformin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• 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.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D., Ph.D.

Study Record Dates

• First Submitted: November 24, 2013
• First Posted: December 9, 2013
• Study Start: December 1, 2013
• Primary Completion: February 1, 2017
• Study Completion: December 1, 2017
• Last Updated: February 5, 2019

Record last verified: 2019-02

Locations

CN (1)