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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT01125449
• Other study ID #: L500HD
• Status: Suspended
• Phase: Phase 2
• First received: May 16, 2010
• Last updated: August 25, 2012
• Start date: January 2011
• Est. completion date: December 2014

Study information

• Verified date: August 2012
• Source: Situs Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 30
• Est. completion date: December 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Desmoplastic Small Round Cell Tumor
• Multiple Myeloma
• Sarcoma

Intervention

Drug:
• Ascorbic acid (vitamin C)
Intravenous administration of up to 1.5gm/kg of ascorbic acid, twice weekly for up to 12-weeks.

Locations

Country	Name	City	State
United States	Situs Cancer Research Center	Rogers	Arkansas

Sponsors (1)

Lead Sponsor	Collaborator
Situs Cancer Research Center

Country where clinical trial is conducted

United States, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. doi: 10.1073/pnas.0804226105. Epub 2008 Aug 4. — View Citation

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. doi: 10.1158/1078-0432.CCR-09-1713. Epub 2010 Jan 12. — View Citation

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. — View Citation

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. — View Citation

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. doi: 10.1093/annonc/mdn377. Epub 2008 Jun 9. Erratum in: Ann Oncol. 2008 Dec;19(12):2095. — View Citation

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. doi: 10.1016/j.freeradbiomed.2009.04.001. Epub 2009 Apr 8. — View Citation

Mikirova NA, Ichim TE, Riordan NH. Anti-angiogenic effect of high doses of ascorbic acid. J Transl Med. 2008 Sep 12;6:50. doi: 10.1186/1479-5876-6-50. — View Citation

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. — View Citation

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. — View Citation

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. doi: 10.1016/j.metabol.2008.09.023. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of treatment	Efficacy of treatment will be evaluated at 12-weeks. Efficacy is evaluated using RECIST criteria to determine disease response by CT scan interpretation	12-weeks	No
Secondary	Quality of Life	Quality of life during treatment will be measured using FACT questionnaires.	12-weeks	No