A Phase 2 Trial of High-dose Ascorbate for Pancreatic Cancer (PACMAN 2.1)

One of the standard treatments for metastatic pancreatic adenocarcinoma is nab-paclitaxel
with gemcitabine. This standard therapy administers chemotherapy once per week for three
weeks; patients then get a 'rest week' to complete the cycle (1 cycle = 4 weeks).

This study adds 75 grams of ascorbate (vitamin C, sometimes called pharamcological ascorbate
because the dose is so high) to standard therapy. The ascorbate is administered intravenously
- through a vein in the arm.

Participants in the control group will:

- receive gemcitabine and nab-paclitaxel chemotherapy, which is standard for their cancer.

- undergo imaging which is standard for their cancer and therapy. This can include CT
scans, PET scans, and X-rays

Participants in the intervention group will:

- receive 75 grams of ascorbate 3 times per calendar week for each week of the
chemotherapy cycle.

- undergo imaging which is standard for their cancer and therapy. This can include CT
scans, PET scans, and X-rays

- provide blood samples to determine the biological effects, if any, the ascorbate has on
the body during therapy.

This active therapy portion lasts until the disease progresses and a new treatment needs to
be adopted - this can be months to years. If disease progresses, participants go back to
standard follow-up for their caner and the new/additional therapy their doctors prescribe.

However, it is very important we remain in contact with participants; they will have
life-long follow-up for this study.

Inclusion Criteria:

- Pathologic diagnosis (cell samples, biopsy, brushing, surgical sample) of
adenocarcinoma of the pancreas. The tissue sample can be from a metastatic location,
like a lymph node.

- Metastatic or node positive disease

- A physician must deem the patient medically fit for chemotherapy

- The patient must have failed initial therapy or be ineligible for definitive curative
therapy (e.g., surgical excision, radiation therapy)

- A platelet count of at least 100,000 cells per mL

- A creatinine level of less than 1 1/2 times the upper limit of normal for the local
lab test, or, a creatinine clearance of at least 60 mL/(min*1.73m2)

- Not pregnant

- Commit to using birth control during the study (all participants)

Exclusion Criteria:

- Prior chemotherapy to treat the metastatic disease

- Other therapy (including radiation) within the past 4 weeks

- Side effects from prior therapies that are still deemed moderate to severe by a
physician

- Glucose-6-phosphate dehydrogenase (G6PD) deficiency

- Patients actively receiving insulin

- Patients requiring daily finger-stick blood glucose measurements

- Patients who are on the following drugs and cannot have a substitution (or who decline
the substitution):

- warfarin

- flecainide

- methadone

- amphetamines

- quinidine

- chlorpropamide

- An active cancer, other than the pancreatic cancer, that requires treatment.

- Enrolled in another therapeutic clinical trial

- Uncontrolled, intercurrent illness

- HIV positive individuals undergoing therapy due to known drug:drug interaction between
antiretroviral drugs and high-dose ascorbate therapy

If all of the above are met, the potential participant will receive a 15 gram challenge
dose of ascorbate via intravenous infusion. This is the final screening procedure.