Safety & Efficacy Study of Gemcitabine...With High Dose IV Vit. C (HDIVC)
Condition: Metastatic Adenocarcinoma of the Pancreas
MeSH terms: Adenocarcinoma
Intervention: Gemcitabine, Intravenous and oral Ascorbic Acid (Vitamin C)
Intervention description: Weeks 1,2,3: IV Gemcitabine 1000 mg / m² over 30 minutes followed by HDIVC 1.2 g / kg: 1.2 g/kg over 90 minutes for a dose ≤90 g and over 120 minutes for a dose >90g followed by 0.3 g / kg over 120 minutes; Week 4: no treatment.
Intervention MeSH terms: Ascorbic Acid; Gemcitabine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      -  The combination of gemcitabine and HDIVC is safe and may favorably change the clinical
           course for an individual patient.

        -  The combination of gemcitabine and HDIVC is synergistic in anti-tumor effect as seen in
           preclinical models, where HDIVC creates a pro-oxidative effect that adds to the
           anti-tumor effect of gemcitabine.

        -  The combination of gemcitabine and HDIVC may improve Progression Free Survival (PFS).

        -  The dosage schema of 1.2 g /kg bolus infusion followed by lower dose of 0.3 g / kg
           infusion may create sustained elevation in Vitamin C plasma levels for increased
           cytotoxic effect.

        -  The addition of HDIVC & oral supplementation of Vitamin C to standard treatment with
           gemcitabine may improve quality of life for patients with comparison to prior to
           treatment start of this protocol.

        -  CA 19-9 and inflammatory markers may show trends for patients in this trial.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient ≥ 18 years of age

          -  Biopsy proven adenocarcinoma of the pancreas

          -  Evidence of metastatic disease

          -  Received at least 1 prior chemotherapy treatment regimen with disease progression

          -  May have had any prior chemotherapy regimen including any gemcitabine based regimen or
             FOLFIRINOX

          -  May have participated in a prior study protocol

          -  May have had prior treatment with HDIVC

          -  Anticipated survival of at least 3 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status = 0,1, or 2

          -  The patient must have screening laboratory: ANC ≥ 1,500/mm3, Hemoglobin > 8g/dL,
             Platelets ≥ 100,000/mm3, Total Bilirubin < 1.5mg/dL, Creatinine ≤ 1.5mg/dL,
             Transaminases < 2.5 x upper limit of normal, Urine Uric Acid < 1.000 mg/d, Urine pH <
             6, Urine microscopic negative for oxalates (if positive, reflex urinary oxalates <
             60mg/d), PT INR ≤ 1.5, unless patient is on full dose warfarin

          -  Glucose-6-phosphate dehydrogenase deficiency (G6PD) normal status via blood test The
             fluorescent spot test is the simplest, most reliable, and most sensitive of the G6PD
             screening tests

          -  Willingness to undergo central line placement and able to manage care of the entry
             site safely

          -  Willingness to adhere to supplemental oral dose regimen of ascorbic acid 500mg taken
             twice daily

          -  All other nutritional supplements would be discontinued for the duration of the trial
             except for pancreatic enzymes and probiotics

          -  Patients must be able to take food orally or have a peg tube for feeding

          -  Able to give consent for protocol participation

        Exclusion Criteria:

          -  Glucose-6-phosphate dehydrogenase deficiency (G6PD)

          -  Renal insufficiency : serum creatinine of > 1.5 mg /dl or evidence of oxalosis by
             urinalysis prior to enrollment and prior to each HDIVC infusion

          -  Documentation or report of history of kidney stones or urinary oxalosis.

          -  Co-morbid condition that would affect survival: congestive heart failure, unstable
             angina, myocardial infarction within 6 weeks of study, uncontrolled blood sugars of >
             300 mg / dl, patients with known chronic active hepatitis or cirrhosis

          -  Currently active second malignancy

          -  Chronic hemodialysis

          -  Iron overload/ Hemochromatosis: Ferritin > 500 ng / ml

          -  Wilson's disease

          -  Pregnant or lactating female (pre- menopausal females will undergo pregnancy test
             prior to administration of protocol drugs throughout treatment cycles during this
             study)

          -  Aspirin use exceeding 81 mg per day

          -  Acetaminophen use exceeding 2 g per day

          -  Known brain metastasis

          -  Active tobacco smokers

          -  Treatment with the combination of HDIVC and gemcitabine previously