Gemcitabine, Ascorbate, Radiation Therapy for Pancreatic Cancer, Phase I

Inclusion Criteria:

* Patients must have histologically or cytologically diagnosed pancreatic adenocarcinoma. Documentation of disease extent by CT scan is required. Radiologically measurable disease is not required.
* Age ≥ 18 years
* ECOG performance status 0, 1, or 2 (Karnofsky \> 50%).
* A complete blood count and differential must be obtained within 21 days prior to radiation fraction 1, with adequate bone marrow functions as defined below:

  * Absolute neutrophil count (ANC) ≥ 1500 cells per mm3
  * Platelets ≥ 100,000 per mm3
  * Leukocytes ≥ 3,000 per mm3
* Serum blood chemistries within 21 days of radiation fraction 1, as defined below:

  * Creatinine ≤ 1.5 x UIHC upper limit of normal or creatinine clearance of at least 60 ml/min/1.73 m2 for patients with creatinine levels above institutional normal.
  * Total bilirubin ≤ 2 x UIHC upper limit of normal
  * ALT ≤ 2.5 times the UIHC upper limit of normal
  * AST ≤ 2.5 times the UIHC upper limit of normal
  * PT/INR within normal limits (UIHC)
* Tolerate one test dose (15g) of ascorbate.
* Not pregnant.
* Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

* G6PD (glucose-6-phosphate dehydrogenase) deficiency.
* Prior abdominal radiotherapy that would result in overlap of fields. The treating radiation oncologist should review prior RT fields as available.
* Adjuvant therapy (including radiation therapy) within 2 calendar weeks. Toxicities from prior therapy for the malignancy should resolve to grade 1 or less.
* Patients actively receiving insulin are excluded.
* Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide. High dose ascorbate may affect urine acidification and, as a result, may affect clearance rates of these drugs.
* Second malignancy other than non-melanoma skin cancers within the past 5 years.
* Other investigational agents/therapy with the intention to treat the disease under study (observational or imaging trials are acceptable).
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness/social situations, or any other condition that would limit compliance with study requirements as determined by study team members.
* Pregnant or lactating women: The risks of radiation and chemotherapy to a fetus are well documented.
* Known HIV-positive individuals. High-dose ascorbate acid is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral drugs. A clinical trial designed to address these interaction issues is more appropriate than this phase 1 study.