Clinical trial NCT01364805: New Treatment Option for Pancreatic Cancer
Official title: Translation of in Vitro and in Vivo Ascorbate Research Into a New Treatment Option for Pancreatic Cancer: Phase I/IIa Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreatic Cancer
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
Collaborators: name: Lotte & John Hecht Memorial Foundation
name: University of Kansas Medical Center
First posted: 2011-06-02
Enrollment: 14
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In the United States, approximately 30,000 new cases of pancreatic cancer are diagnosed each year and an almost equal number of deaths are related to this cancer. Different types of chemotherapeutic treatments are used that target different parts of the cancer cell with some success, but there is room for other treatment options.

It is known that people with cancer are using high doses of intravenous vitamin C also known as ascorbate, as a cancer treatment and this is occurring frequently. When Vitamin C is given in this manner, it is not taken by mouth; instead, it enters your body through an IV (intravenous) site, or tube that is inserted through a needle into your vein. If you have a port-a-cath in place, the IV will be given using your port. When Vitamin C enters your body through an IV site, it is known that it acts like a drug and not a vitamin. It produces a substance around the cancer cells called hydrogen peroxide. It has been seen in animal research studies that hydrogen peroxide kills the cancer cells while leaving the normal cells unharmed.

Currently the FDA does not approve the use of high-dose intravenous Vitamin C as a cancer treatment. The use of intravenous Vitamin C in this study is experimental. Furthermore, it is important to know that we do not expect the intravenous Vitamin C given in this study to be healing for the treatment of your cancer.

Detailed description: The purpose of this study is to determine if it is safe to give Vitamin C by the vein at high doses to people with pancreatic cancer and if Vitamin C interferes with how well the chemotherapy works on cancer cells. This study will also look at how the body processes of Vitamin C. This study will also help researchers to learn more about long Vitamin C stays in the blood stream, and how rapidly it is used by the body.

Eligibility criteria: Inclusion Criteria:

* Patients must be 21 years of age or older and have histologically or cytologically diagnosed carcinoma of the pancreas defined as locally advanced or metastatic and if locally advanced, not eligible for surgical resection
* The patient must screened for eligibility and have care approved by treating oncologist; the oncology care is to be dictated by the oncology team and patient and will include gemcitabine chemotherapy.
* ECOG Performance Status 0-2 Eastern Cooperative Oncology Group Performance Status Grade 0 = Fully active, able to carry on all pre-disease activities without restriction Grade 1= Restricted in physical strenuous activity but ambulatory and able to carry out work of a light or sedentary nature e.g. light housework, office work Grade 2 = Ambulatory and capable of all self care but unable to carry out any work activities, up and about more than 50% of waking hours
* Laboratory: ANC ≥1,500/mm3, Hemoglobin \> 8g/dL, platelet ≥ 1000,000/mm3, total bilirubin ≤ 1.5 mg/dL (in the absence of neoplastic involvement), creatinine ≤2.0 mg/dL, transaminase (AST/ALT) ≤2.5X upper limit, urine uric acid \< 1,000mg/d, urine pH \<6, urine oxalate \<60 mg/d.
* Patients who have no language barrier, are cooperative, and can give informed consent before entering the study after being informed of the medications and procedures to be used in this study may participate.

Exclusion Criteria:

* Glucose-6-phosphate-dehydrogenase (G6PD) deficiency
* History of oxalate renal calculi; urine oxalate level \> 60 mg/d at baseline
* History of bleeding disorder, iron overload or hemochromatosis
* Prior chemotherapy or currently receiving chemotherapy or radiation therapy or enrolled in other trials currently or in the preceding 1 month.
* Patients with evidence of a significant psychiatric disorder by history/examination that would prevent completion of the study will not be allowed to participate.
* ECOG Performance Status of 3-4. Grade 3 = capable of only limited self care, confined to bed or chair more than 50% of waking hours. Grade 4 = completely disabled. Cannot carry on any self care. Totally confined to bed or chair.)
* Co-morbid condition that would affect survival: end stage congestive heart failure, unstable angina, myocardial infarction within 6 weeks of study, uncontrolled blood sugars ≥ 300 mg/dL, patients with known chronic active hepatitis or cirrhosis.
* Patients who consume an excess of alcohol or abuse drugs (an excess of alcohol is defined as more than four of any one of the following per day: 30mL distilled spirits, 340mL beer, or 120mL wine) will not be allowed.
* Patients who smoke tobacco products will not be allowed to participate.

Primary outcomes:
measure: Determine safety of combined gemcitabine chemotherapy with IV ascorbate.
timeFrame: 12 months
Secondary outcomes:
measure: Assess pharmacokinetic and pharmacodynamic interactions when adding IV AA to front-line gemcitabine chemotherapy in the treatment of locally advanced or metastatic pancreatic cancer not eligible for surgical resection.
timeFrame: 12 months
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
Study officials:
affiliation: University of Kansas Medical Center
name: Jeanne Drisko, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Polireddy K, Dong R, Reed G, Yu J, Chen P, Williamson S, Violet PC, Pessetto Z, Godwin AK, Fan F, Levine M, Drisko JA, Chen Q. High Dose Parenteral Ascorbate Inhibited Pancreatic Cancer Growth and Metastasis: Mechanisms and a Phase I/IIa study. Sci Rep. 2017 Dec 7;7(1):17188. doi: 10.1038/s41598-017-17568-8.