This phase II trial studies how well metformin hydrochloride, leucovorin calcium, fluorouracil, and oxaliplatin work in treating patients with metastatic pancreatic cancer. Metformin hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving metformin hydrochloride together with combination chemotherapy may kill more tumor cells
PRIMARY OBJECTIVES: I. To determine if metformin (metformin hydrochloride) when added to FOLFOX ( leucovorin calcium, fluorouracil, oxaliplatin) improves overall survival in patients with metastatic pancreatic cancer. SECONDARY OBJECTIVES: I. To assess response rate (RR). II. To assess progression free survival (PFS). III. To assess toxicity in patients with metastatic pancreatic cancer receiving FOLFOX and metformin. IV. To identify tumor/serum correlative markers. OUTLINE: Patients receive metformin hydrochloride orally (PO) twice daily (BID) on days 1-7 for an introductory period before the addition of FOLFOX. After the introductory period, patients will continue metformin twice daily and FOLFOX therapy comprising leucovorin calcium intravenously (IV) over 120 minutes, fluorouracil IV continuously over 46 hours, and oxaliplatin IV over 120 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for periodically.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
Median Overall Survival (OS)
Calculated using Kaplan Meier methods and the median will be estimated assuming an exponential distribution.
Time frame: Time from first day of treatment to death from any cause, assessed up to 1 year
Response Rate (RR) Objective Tumor Response Based on Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans According to Response Evaluation Criteria in Solid Tumors (RECIST)
CBR is the number of participants of the total analysis population who experience confirmed complete (CR) or partial response (PR) per RECIST CR = all detectable tumor has disappeared PR = a \>=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum Stable Disease (SD) = small changes that do not meet previously given criteria. Progressive disease (PD) = a \>=20% increase in target lesions The true response rate of the combination therapy for this patient population will be estimated based on the number of response using a binomial distribution and its confidence intervals will be estimated using Wilson's method.
Time frame: 1 year
Clinical Benefit Rate (CBR) Based on Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans According to RECIST
CBR is the number of participants of the total analysis population who experience a CR, PR, or SD per RECIST CR = all detectable tumor has disappeared PR = a \>=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum SD = small changes that do not meet previously given criteria. PD = a \>=20% increase in target lesions
Time frame: 1 year
Progression Free Survival According to RECIST 1.1 Criteria
Calculated using Kaplan Meier methods and the median will be estimated assuming an exponential distribution.
Time frame: Time from first day of treatment received to the earlier documented disease progression or death from any cause, assessed up to 1 year
Number of Grade 3 and 4 Toxicities According to NCI CTCAE Version 4.0
The toxicity profile of the combination will be tabulated.
Time frame: Up to 1 year
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