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

This clinical trial adds high-dose ascorbate (vitamin C) to the standard of care regimen for metastatic pancreatic adenocarcinoma (a type of pancreatic cancer). Subjects are randomized between a control group (standard treatment) and an intervention group (pharmacologic ascorbate in addition to the standard treatment).

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.

Eligibility Criteria:
Inclusion Criteria:

* Pathologic diagnosis (cell samples, biopsy, brushing, surgical sample) of adenocarcinoma of the pancreas. Cancer from the Ampullae of Vater is also eligible. The tissue sample can be from a metastatic location, like a lymph node.
* Metastatic or node positive disease
* One cancer site, that did not receive radiation therapy, that is at least 1 cm in size when looking at it by CT scan (CAT scan)
* Recommended to receive gemcitabine and nab-paclitaxel
* 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 or who are currently recommended to receive insulin by a doctor
* 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
* Women who are nursing