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Ascorbic Acid

Gemcitabine

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Vitamin C

Gemcitabine (1000 mg/m2) weekly for three weeks and then one week off. Ascorbic acid, given twice weekly, escalating doses weekly. Week 1: 15 grams ascorbic acid per infusion Week 2: 25 grams ascorbic acid per infusion Week 3: 50 grams ascorbic acid per infusion Week 4: 75 grams ascorbic acid per infusion Week 5: 100 grams ascorbic acid per infusion

Ascorbic acid infusion dose is maintained at the level that provides a serum level of 350-400 mg/dL.

Gemcitabine with escalating ascorbic acid

Joseph J Cullen, M.D.

This study is designed to determine the maximum tolerated dose of vitamin C when given with a standard chemotherapy for people who have metastatic pancreatic cancer.

This is a phase I, dose-escalating study of ascorbic acid (vitamin C) designed to determine the maximum tolerated dose of vitamin C or, if well tolerated, the dose required to obtain a desired ascorbic acid plasma concentration.

Because this is a phase I study, prospective subjects should have advanced disease (i.e., metastasis) and have failed other curative therapies (or, are unable to receive curative therapies due to comorbidities or stage of disease).

A Research Trial of High Dose Vitamin C and Chemotherapy for Metastatic Pancreatic Cancer

A Phase I Trial of Ascorbic Acid and Gemcitabine for the Treatment of Metastatic Pancreatic Cancer

University of Iowa

Holden Comprehensive Cancer Center

Joseph J. Cullen

Professor

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 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)

Joseph J Cullen, MD

This is a phase II study. It is designed to provide information about if high-dose ascorbate (vitamin C) increases survival for pancreatic cancer patients. The hypothesis is that vitamin C is well tolerated and increases cancer treatment effectiveness, lengthening survival time for patients with advanced pancreatic cancer.

Adenocarcinoma of the pancreas is the fourth leading cause of cancer death in the United States and is increasing in incidence; the prognosis remains dismal. We propose to investigate an entirely new approach, using pharmacological ascorbate, combined with Gemcitabine, to treat this cancer. Intravenous ascorbate (i.e., ascorbic acid, vitamin C), but not oral ascorbate, produces high plasma concentrations, which are in the range that can be cytotoxic to tumor cells. Though ascorbate has been utilized in cancer therapy, few studies have investigated intravenous deliver of ascorbate. Preliminary studies from our group have demonstrated that ascorbate induces oxidative stress and cytotoxicity in pancreatic cancer cells; this cytotoxicity appears to be greater in tumor vs. normal cells. We hypothesize that production of H2O2 mediates the increased susceptibility of pancreatic cancer cells to ascorbate-induced metabolic oxidative stress. Gemcitabine is the standard chemotherapy drug used to treat pancreatic cancer.

Clinical Trial of High-dose Vitamin C for Advanced Pancreatic Cancer

Pharmacological Ascorbate for the Control of Metastatic and Node-Positive Pancreatic Cancer (PACMAN): A Phase II Trial

Time to event outcome measure (death), measured in days from cycle 1 day 1.

Time-to-event outcome measure (initial disease progression) measured in days from cycle 1 day 1 to day of first progression as defined by RECIST criteria from NCI.

Adverse events linked to ascorbate will be categorized and quantified using CTCAE v4 at the bottom of each cycle. Incidence and frequency will be compared to scientific literature

F2-isoprostane is a marker of systemic oxidative stress.

Ascorbate levels will be taken at the bottom of each cycle to assess therapeutic dose window.

Susan L Bader Foundation of Hope

National Cancer Institute (NCI)

Professor of Surgery

Adverse event reporting is consistent with the definition provided by clinicaltrials.gov

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)

Gemcitabine With Escalating IV Ascorbate

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

There was only one treated participant. Conclusions cannot be drawn from these data due to limited sampling size.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Research Trial of High Dose Vitamin C and Chemotherapy for Metastatic Pancreatic Cancer	NCT01049880	Pancreatic Neop...	Gemcitabine wit...	18 Years -	University of Iowa
A Research Trial of High Dose Vitamin C and Chemotherapy for Metastatic Pancreatic Cancer	NCT01049880	Pancreatic Neop...	Gemcitabine wit...	18 Years -	University of Iowa
Clinical Trial of High-dose Vitamin C for Advanced Pancreatic Cancer	NCT01515046	Pancreatic Neop... Pancreatic Canc...	Gemcitabine wit...	18 Years -	University of Iowa

Spots Global Cancer Trial Database for gemcitabine with escalating ascorbic acid