Study of High Dose Intravenous (IV) Ascorbic Acid in Measurable Solid Tumor Disease

Condition(s) targeted: Sarcoma; Adenocarcinoma; Carcinoma; Multiple Myeloma; Desmoplastic Small Round Cell Tumor

Intervention: Ascorbic acid (vitamin C) (Drug)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: Situs Cancer Research Center

Official(s) and/or principal investigator(s):
G D Murphy, MD, Principal Investigator, Affiliation: Situs Cancer Research Center
J Bolt, PhD, Study Director, Affiliation: Situs Cancer Research Center

Overall contact:
Nikki Sailer, CRC, Phone: 479-636-0500, Ext: 222

The study is designed to determine if high doses of intravenous ascorbic acid (vitamin C) can be effective in managing solid tumor diseases. Secondary goals are determination of any palliative effects and improvement of quality of life of patients.

Official title: Phase 2 Study of High Dose Ascorbic Acid in Solid Tumor Disease

Study design: Allocation: Non-Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Efficacy of treatment

Secondary outcome: Quality of Life

Detailed description: Ascorbic acid has demonstrated selective cytotoxicity in cancer cells in vitro, while sparing normal cells from its peroxidative effects. This study will examine the effect, if any, of the drug when dosed in patients at a level sufficient to achieve transient serum states of 400mg/dl. Safety of the drug has been shown in a Phase I study when dosed as high as 1. 5gm/kg. Patients will be treated twice weekly for 12 weeks (24-cycles) and evaluated for response using RECIST criteria. Patients showing stable disease or objective response will remain on study for up to one year or until absence of measurable disease or disease progression.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 18 years or older at time of entry on study

- Disease extent confirmed and documented by CT scan within 45 days of entry on study

- normal glucose 6-phosphate dehydrogenase

- no current calcium oxalate nephrolithiasis with the potential to reduce urinary flow

- ability to understand the informed consent process and to give informed consent to

treatment

- measurable solid tumor neoplastic disease (using RECIST criteria)

- life expectancy greater than 8-weeks

- will agree to undergo central line placement (examples are: port-a-catheter, central

venous catheter, percutaneously inserted central catheter [PICC] line placement). Patient or regular caregiver must be able to maintain flush central line as directed by study physician. (Study center will provide periodic site dressing changes as required)

- Failed curative therapy or patient ineligible for definitive curative therapy

- Karnofsky performance status of at least 40

Exclusion Criteria:

- any clinically relevant abnormal findings in physical examination, clinical

chemistry, haematology, urinalysis, vital signs, or ECG at baseline which, in the opinion of the investigator, may put the subject at risk because of his/her participation in the study

- use of any nicotine product including nicotine patches/gum

- unstable angina not well managed with medication

- history of calcium oxalate stone formation

- pregnancy or nursing of an infant

- any psychiatric disorder by history or examination that would prevent completion of

the study

Nikki Sailer, CRC, Phone: 479-636-0500, Ext: 222

Situs Cancer Research Center, Rogers, Arkansas 72756, United States

Related publications:

Mikirova NA, Ichim TE, Riordan NH. Anti-angiogenic effect of high doses of ascorbic acid. J Transl Med. 2008 Sep 12;6:50.

Duconge J, Miranda-Massari JR, Gonzalez MJ, Jackson JA, Warnock W, Riordan NH. Pharmacokinetics of vitamin C: insights into the oral and intravenous administration of ascorbate. P R Health Sci J. 2008 Mar;27(1):7-19. Review.

Duconge J, Miranda-Massari JR, González MJ, Taylor PR, Riordan HD, Riordan NH, Casciari JJ, Alliston K. Vitamin C pharmacokinetics after continuous infusion in a patient with prostate cancer. Ann Pharmacother. 2007 Jun;41(6):1082-3. Epub 2007 May 22. No abstract available.

Riordan HD, Casciari JJ, González MJ, Riordan NH, Miranda-Massari JR, Taylor P, Jackson JA. A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients. P R Health Sci J. 2005 Dec;24(4):269-76.

Du J, Martin SM, Levine M, Wagner BA, Buettner GR, Wang SH, Taghiyev AF, Du C, Knudson CM, Cullen JJ. Mechanisms of ascorbate-induced cytotoxicity in pancreatic cancer. Clin Cancer Res. 2010 Jan 15;16(2):509-20. Epub 2010 Jan 12.

Levine M, Espey MG, Chen Q. Losing and finding a way at C: new promise for pharmacologic ascorbate in cancer treatment. Free Radic Biol Med. 2009 Jul 1;47(1):27-9. Epub 2009 Apr 8. No abstract available.

Robitaille L, Mamer OA, Miller WH Jr, Levine M, Assouline S, Melnychuk D, Rousseau C, Hoffer LJ. Oxalic acid excretion after intravenous ascorbic acid administration. Metabolism. 2009 Feb;58(2):263-9.

Hoffer LJ, Levine M, Assouline S, Melnychuk D, Padayatty SJ, Rosadiuk K, Rousseau C, Robitaille L, Miller WH Jr. Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann Oncol. 2008 Nov;19(11):1969-74. Epub 2008 Jun 9. Erratum in: Ann Oncol. 2008 Dec;19(12):2095.

Chen Q, Espey MG, Sun AY, Lee JH, Krishna MC, Shacter E, Choyke PL, Pooput C, Kirk KL, Buettner GR, Levine M. Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc Natl Acad Sci U S A. 2007 May 22;104(21):8749-54. Epub 2007 May 14.

Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, Shacter E, Levine M. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13604-9. Epub 2005 Sep 12.

Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, Khosh DB, Drisko J, Levine M. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11105-9. Epub 2008 Aug 4.

Ohno S, Ohno Y, Suzuki N, Soma G, Inoue M. High-dose vitamin C (ascorbic acid) therapy in the treatment of patients with advanced cancer. Anticancer Res. 2009 Mar;29(3):809-15. Review.

Starting date: June 2010
Last updated: May 17, 2010