High Dose Ascorbic Acid (AA) + Nanoparticle Paclitaxel Protein Bound + Cisplatin + Gemcitabine (AA NABPLAGEM) in Patients Who Have Metastatic Pancreatic Cancer

Pancreatic cancer continues to be a very lethal disease. It was estimated that in 2016,
53,070 Americans would be diagnosed with pancreatic ductal adenocarcinoma (PDA), and 41,780
would die from the disease. This makes pancreatic cancer the third leading cause of death
from cancer in the US.

PDA is the twelfth most common cancer in the world with 338,000 new cases diagnosed in 2012.
It is estimated that worldwide there will be > 300,000 deaths from pancreatic cancer.
Furthermore unfortunately PDA is projected to be the second leading cause of death from
cancer in the US by 2030.

Detection of pancreatic cancer has notoriously been very late in the disease and therefore
the 5-year survival rate is only 8%, which is actually a slight improvement over the last few
years. Right now the only potential cure for pancreatic cancer is surgical resection (if the
disease is caught early). However only about 20% of PDA patients are eligible for potentially
curable resection and unfortunately most (> 80%) have recurrence of their cancer within 2
years of resection, and those recurrences are almost universally fatal.

Recently it has been shown that there are regimens that actually improve survival for
patients with advanced stage IV PDA. Conroy and colleagues have developed the Folfirinox
regimen, which in a large randomized trial improved survival over gemcitabine as a single
agent. Von Hoff and colleagues developed the nanoparticle albumin (nab) associated paclitaxel
plus gemcitabine regimen which improved survival over single agent gemcitabine. Even more
recently Jameson and colleagues have presented a combined regimen of nab-paclitaxel +
gemcitabine + cisplatin in a small 24 patient phase Ib/II trial which showed a response rate
of 71% with 2 patients having complete response, a 1-year survival of 65% and a median
survival of 16+ months.

While there have been multiple investigators and investigations into the use of ascorbic acid
for patients with cancer (see ClinTrials.gov), its use has generally not been found to be of
help for patients particularly when given orally - e.g. 10 grams daily.

Inclusion Criteria:

- Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma (with
measurable disease according to RECIST 1.1 criteria).

- Adequate organ function

Exclusion Criteria:

- Patients must have received no previous radiotherapy, surgery, chemotherapy or
investigational therapy for the treatment of metastatic disease. Prior treatments in
the adjuvant setting with gemcitabine and/or 5-FU or gemcitabine administered as a
radiation sensitizer are allowed, provided at least 6 months have elapsed since
completion of the last dose

- Palliative surgery and/or radiation treatment less than 4 weeks prior to initiation of
study treatment.

- Exposure to any investigational agent within 4 weeks prior to initiation of study
treatment.

- Patients who need constant use of finger stick blood glucose monitoring for tight
control of their diabetes

- Any person with a G6PD deficiency

- History of renal oxalate stones

- Patient is taking acetaminophen at any dose, or any medication that contains
acetaminophen within 72 hours of first dose of ascorbic acid.

- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer.

- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Patients with previously treated brain metastases may participate provided
they are stable (without evidence of progression by imaging for at least four weeks
prior to the first dose of trial treatment and any neurologic symptoms have returned
to baseline), have no evidence of new or enlarging brain metastases, and are not using
steroids for at least 7 days prior to trial treatment. This exception does not include
carcinomatous meningitis which is excluded regardless of clinical stability.

- Is pregnant or breastfeeding

- Current, serious, clinically significant cardiac arrhythmias or receiving a digitalis
derivative.