Intervention: Gemcitabine
Trial phase: Phase 2
ATC code: L01BC05
SMILES: Nc1ccn([C@@H]2O[C@H](CO)[C@@H](O)C2(F)F)c(=O)n1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 1
Group description: Gemcitabine (1000 mg/m2) weekly for three weeks and then one week off. Ascorbic Gemcitabine (1000 mg/m2) weekly for three weeks and then one week off.

Ascorbate (vitamin C) given twice weekly, escalating doses weekly. Week 1: 15 grams ascorbate / infusion for two infusions. Doses are then escalated in 25 gram increments until therapeutic window is achieved (350 mg/dL or above). Dose is then held at that level for the full cycle.

Gemcitabine with escalating ascorbic acid: Gemcitabine 1000 mg/m2 weekly for 3 weeks with one week off (this is 1 cycle)

Ascorbate dose is targeted to achieve plasma level of 350 mg/dL. Infusions are given twice weekly, each week of a cycle (4 weeks to a cycle)
Eligibility criteria:
Inclusion Criteria:

Patients must have a cytological or histological diagnosis of adenocarcinoma arising in the pancreas. Diagnosis from metastatic sampling is acceptable.
Disease must be measured radiologically.
Failed initial therapy or ineligible for definitive curative therapy.
If prior treatment included radiation therapy, recurrent disease must be outside of the targeted volume.
Age ≥ 18 years
ECOG performance status 0-2 (Karnofsky > 50%, see Appendix A).

Patients must have normal organ and marrow function as defined below:

leukocytes ≥ 3,000/mm3
absolute neutrophil count ≥ 1,500/mm3
platelets ≥ 100,000/mm3
total bilirubin < 2x institutional upper limit of normal
AST(SGOT) < 3x institutional upper limit of normal OR < 5x institutional upper limit of normal for patients presenting with liver metastases
ALT (SGPT) < 3x institutional upper limit of normal OR < 5x institutional upper limit of normal for patients presenting with liver metastases
PT/INR within normal institutional limits, unless patient is on warfarin or other antithrombotic agents
creatinine < 1.5 X institutional upper limit of normal OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
Not pregnant. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Prior chemotherapy to treat metastatic disease.
Adjuvant therapy (including radiation therapy) within 4 calendar weeks.
Unresolved toxicities from prior therapy for the malignancy.
G6PD (glucose-6-phosphate dehydrogenase) deficiency.
Second malignancy other than non-melanoma skin cancers within the past 5 years.
Excess consumption of alcohol where an excess of alcohol is defined as more than four of any one of the following per day: 30 mL distilled spirits, 340 mL beer, or 120 mL wine.
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 chemotherapy to a fetus/infant are well documented.