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New Treatment Option for Pancreatic Cancer

Primary Purpose

Pancreatic Cancer

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Intravenous Vitamin C

Gemcitabine

About this trial

This is an interventional treatment trial for Pancreatic Cancer

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Kansas Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PK Intravenous Vitamin C and Gemcitabine

Arm Description

Week 1: 2 visits for escalating doses of intravenous ascorbic acid (IV C). First dose 25 gm followed by 50 gm 2nd visit. Week 2: 3 visits escalating doses of IV C, 75 grams, 100 grams, and 125 grams. Week 3: 2 visits pharmacokinetic evaluation of intravenous ascorbic acid alone at 125 grams; return to the infusion clinic the following morning for a 24 hour blood draw; 2nd visit receive the first infusion of gemcitabine chemotherapy for PK evaluation of gemcitabine alone. Week-4: gemcitabine and IV C co-administered for pharmacokinetics of both drugs to assess for PK variability related to drug-drug interactions. Subjects will return to the infusion clinic the following morning for 24 hour blood draw.

Outcomes

Primary Outcome Measures

Determine safety of combined gemcitabine chemotherapy with IV ascorbate.

This will be accomplished by enrolling up to 14 participants fitting inclusion criteria into the Phase I portion of the trial: 7 participants will be enrolled at the determined dose levels and if no significant adverse event is identified, then 7 additional participants will be enrolled. Safety will be assessed by obtaining the following evaluations: toxicity graded by the NCI CTCAE v 4.0, urinalysis pre- and post-infusion, ECG, basic metabolic panel, bicarbonate (pH surrogate marker), CBC, and osmolality.

Secondary Outcome Measures

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.

By measuring PK data when combining gemcitabine chemotherapy along with IV ascorbate on the same day, it will be determined if there are reduced gemcitabine levels in the presence of ascorbate. Initially 7 participants will be enrolled and if no significant interaction defined, an additional 7 will be enrolled.

Full Information

NCT ID

NCT01364805

First Posted

May 24, 2011

Last Updated

June 16, 2018

Sponsor

Jeanne Drisko, MD, CNS, FACN

Collaborators

Lotte & John Hecht Memorial Foundation, University of Kansas Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT01364805

Brief Title

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

2. Study Status

Record Verification Date

June 2018

Overall Recruitment Status

Completed

Study Start Date

April 2011 (undefined)

Primary Completion Date

October 2015 (Actual)

Study Completion Date

October 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Jeanne Drisko, MD, CNS, FACN

Collaborators

Lotte & John Hecht Memorial Foundation, University of Kansas Medical Center

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreatic Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PK Intravenous Vitamin C and Gemcitabine

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Intravenous Vitamin C

Other Intervention Name(s)

IV ascorbic acid

Intervention Description

The first 5 study visits will all take place in the General Clinical Research Center (GCRC). During these visits you will receive IV doses of Vitamin C. The dose of Vitamin C will be started at 25 grams and may be increased up to 125 grams over a two week period. There may be changes in the amount of Vitamin C that you receive based on your blood test levels. The study staff will go over this in more detail with you. The amount of fluid you receive depends on the dose and can be from 2 1/3 cups to 5 cups.

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Other Intervention Name(s)

Gemsar

Intervention Description

Participants receive dexamethasone 10 mg as pretreatment antiemetic; may be given ondansetron, granisetron, or dolasetron, per oncologist. Gemcitibane 1,000mg/m2 IV over 30 minutes Q 21 days. Cycle of treatment: infusions once weekly for 2 consecutive weeks followed by 1 week of rest to continue treatment schedule until they experience disease progression or unacceptable toxicity. CR, PR or SD: treatment will be continued for at least 6 cycles. Discontinuation of therapy may be considered if agreed upon by the participant and oncologist. Dose Modifications: If the patient experiences more than one toxicity, each requiring a dose reduction, follow the guidelines that give the largest dose reduction for the drug. Subsequent doses can be adjusted to as low as 500 mg/m2 for gemcitabine.

Primary Outcome Measure Information:

Title

Determine safety of combined gemcitabine chemotherapy with IV ascorbate.

Description

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Description

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeanne Drisko, MD

Organizational Affiliation

University of Kansas Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Kansas Medical Center

City

Kansas City

State/Province

Kansas

ZIP/Postal Code

66160

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

29215048

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.

Results Reference

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New Treatment Option for Pancreatic Cancer

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