Study of High-Dose Intravenous (IV) Vitamin C Treatment in Patients With Solid Tumors

• ClinicalTrials.gov Identifier: NCT00441207
• Recruitment Status: Completed
• First Posted: February 28, 2007
• Last Update Posted: April 23, 2013
• Sponsor: Midwestern Regional Medical Center
• Information provided by (Responsible Party): Chris Stephenson, Midwestern Regional Medical Center

Tracking Information

• First Submitted Date: February 26, 2007
• First Posted Date: February 28, 2007
• Last Update Posted Date: April 23, 2013
• Study Start Date: August 2006
• Actual Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 24, 2010)

• Evaluate the safety and tolerability of high dose IV vitamin C as a monotherapy [ Time Frame: 1-1/2 years ]
• Evaluate the pharmacokinetic profile of IV vitamin C at varying doses [ Time Frame: 1-1/2 years ]

Original Primary Outcome Measures (submitted: February 26, 2007)

• Evaluate the safety and tolerability of high dose IV Vitamin C as a monotherapy
• Evaluate the pharmacokinetic profile of IV Vitamin C at varing doses.

Current Secondary Outcome Measures (submitted: June 24, 2010)

• Determine if vitamin C accumulates with repeated daily therapy by measuring peak and nadir levels [ Time Frame: 1 year ]
• Evaluate patient quality of life [ Time Frame: Duration of Study ]
• Observe patients for clinical and radiological evidence of anti-tumor activity at the end of treatment [ Time Frame: Duration of Study ]

Original Secondary Outcome Measures (submitted: February 26, 2007)

• Determine if vitamin C accumulates with repeated daily therapy by measuring peak and nadir levels.
• Evaluate patient quality of life
• Observe patients for clinical and radiological evidence of anti-tumor activity at the end of treatment.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of High-Dose Intravenous (IV) Vitamin C Treatment in Patients With Solid Tumors
• Official Title: A Phase I Study of High-Dose IV Vitamin C Treatment in Patients With Solid Tumors

Brief Summary

The primary purpose of this study is to evaluate the safety and tolerability of vitamin C (ascorbic acid) given by injection into the vein.

The second and third purpose of conducting this study is to observe any evidence of tumor response to the vitamin C and compare the level of fatigue (weakness), pain control, ability to do things, and quality of life, before and after vitamin C is given.

Detailed Description

Preclinical studies of pharmacologic doses of vitamin C (ascorbic acid, ascorbate) have shown significant anticancer effects in animal models and tissue culture investigations including cytotoxic effects in certain cancer cell lines at micromolar to millimolar concentrations.

Early clinical studies have shown that intravenous and oral doses of vitamin C may improve symptoms and prolong survival in terminal cancer patients. More recent double-blind placebo-controlled studies have shown that oral adminstration of vitamin C provides no benefit to cancer patients. Conversely, intravenous vitamin C administration raises plasma concentrations as high as 14 mM/L, and concentrations of 1-5 mM/L have been found to be selectively cytoxic to tumor cells in vitro.

The proposed Phase I trial with vitamin C should achieve millimolar concentrations of vitamin C that have been shown to kill tumor cells in vitro. The maximum tolerated dose (MTD), PK, possible drug accumulation with repeated dosing, quality of life, pain response, fatigue status, and hints of efficacy in patients with advanced cancer will be examined.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cancer

Intervention

Drug: Ascorbic Acid

Delivered via IV Infusion.

• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 26, 2007): 18
• Original Enrollment: Same as current
• Actual Study Completion Date: July 2010
• Actual Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Primary histological diagnosis of advanced solid tumors (stage 3 and 4) and measurable disease.
• Disease must have progressed for which no available treatment provides clinical benefit.
• 18 years of age or older.
• No scheduled cancer therapy (chemotherapy, hormonal therapy, immune therapy, or radiation therapy) for three months after study entry, and the subject must have had their last therapy at least four (4) weeks prior to entry to this study.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Informed Consent - The patient must be willing and able to sign the informed consent prior to the start of the trial.
• Willingness to comply with the weekly phone calls between office visits.
• Willingness to undergo central line placement (e.g., port-a-catheter, central venous catheter, percutaneously inserted central catheter [PICC] line placement) and able to manage care of the entry site safely.
• Patients must be able to take food orally or have peg tube for feeding.
• Life expectancy of at least 3 months.

Exclusion Criteria:

• Glucose-6-phosphate dehydrogenase deficiency (G6PD) (a relative contraindication)
• Renal insufficiency as evidenced by serum creatinine of ≥ 1.3 mg/dl or evidence of oxalosis by urinalysis.
• Chronic hemodialysis.
• Iron overload (a ferritin > 500 ng/ml).
• Wilson's disease.
• Compromised liver function with evidence of complete biliary obstruction or have a serum bilirubin of 2.0 or liver function tests (AST > 63, ALT > 95) exceeding 1.5 x the upper limit of normal.
• Pregnant or lactating female.
• Current tobacco use.
• Evidence of significant psychiatric disorder by history or examination that would prevent completion of the study or preclude informed consent.
• Aspirin use exceeding 325 mg per day.
• Acetaminophen use exceeding 2 g per day.
• Brain metastases that have not responded to therapy.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00441207
• Other Study ID Numbers: CTCA 06-04; Ascorbic Acid Injection
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Chris Stephenson, Midwestern Regional Medical Center
• Original Responsible Party: Not Provided
• Current Study Sponsor: Midwestern Regional Medical Center
• Original Study Sponsor: Cancer Treatment Centers of America
• Collaborators: Not Provided

Investigators

• Principal Investigator: Christopher Lis; Midwestern Regional Medical Center

• PRS Account: Midwestern Regional Medical Center
• Verification Date: April 2013