Metformin Plus Modified FOLFOX 6 in Metastatic Pancreatic Cancer
Condition: Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage IV Pancreatic Cancer
MeSH terms: Adenocarcinoma; Pancreatic Neoplasms; Carcinoma, Acinar Cell
Intervention: metformin hydrochloride; oxaliplatin; leucovorin calcium; fluorouracil; laboratory biomarker analysis
Intervention description: Given PO; Given IV; Given IV; Given IV; Correlative studies
Intervention MeSH terms: Leucovorin; Metformin; Fluorouracil; Oxaliplatin; Calcium; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed metastatic pancreatic
             adenocarcinoma (or any mixed pathology if adenocarcinoma is predominant)

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as >
             20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT)
             scan

          -  Patient must have not received systemic chemotherapy for metastatic disease; prior
             chemotherapy, radiation therapy, concurrent chemoradiation are allowed if used for
             treatment of non-metastatic disease; prior palliative radiation for symptom management
             is allowed; any chemotherapy must have been completed 4 weeks prior to enrollment; any
             radiotherapy must have been completed 2 weeks prior to enrollment

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Absolute neutrophil count ≥ 1,500/L

          -  Platelets ≥ 100,000/L

          -  Hemoglobin ≥ 9 g/dL

          -  Total bilirubin ≤ 2 mg/dL

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT]/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) ≤
             2.5 x institutional upper limit of normal

          -  Creatinine ≤ 1.5

          -  Women of childbearing potential and men must agree to use adequate contraception
             (double barrier method of birth control or abstinence) prior to study entry and for
             the duration of study participation; should a woman become pregnant or suspect that
             she is pregnant while she or her partner is participating in this study, she should
             inform the treating physician immediately

          -  Subjects must have the ability to understand and the willingness to sign a written
             informed consent document

          -  Patients with diabetes 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:

          -  Chemotherapy within 4 weeks prior to entering the study, radiotherapy within 2 weeks
             prior to entering the study or failure to recover from adverse events due to agents
             administered more than 4 weeks earlier

          -  Prior treatment toxicities must be resolved to ≤ grade 1 according to National Cancer
             Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

          -  Current use of metformin for more than 6 months prior to enrollment on study

          -  Use of any other investigational agents

          -  Patients with untreated brain metastases should be excluded from this clinical trial

          -  History of allergic reactions attributed to compounds of similar chemical or
             biological composition to metformin or oxaliplatin or fluorouracil (5-FU)

          -  Active second primary malignancy or history of second primary malignancy within the
             last 3 years, with the exception of basal cell skin cancers or carcinoma in situ that
             have been adequately treated

          -  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

          -  Pregnant or nursing women

          -  Human immunodeficiency virus (HIV)-positive patients

          -  Chronic or planned acute alcohol use of three or more drinks per day

          -  Metabolic acidosis, acute or chronic, including ketoacidosis