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 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.