Study of High Dose Intravenous (IV) Ascorbic Acid in Measurable Solid Tumor Disease - Full Text View

Purpose

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.

Condition	Intervention	Phase
Sarcoma Adenocarcinoma Carcinoma Multiple Myeloma Desmoplastic Small Round Cell Tumor	Drug: Ascorbic acid (vitamin C)	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase 2 Study of High Dose Ascorbic Acid in Solid Tumor Disease

Resource links provided by NLM:

MedlinePlus related topics: Cancer Vitamin C

Drug Information available for: Ascorbic acid Sodium ascorbate Magnesium ascorbate

Genetic and Rare Diseases Information Center resources: Desmoplastic Small Round Cell Tumor Malignant Mesenchymal Tumor Multiple Myeloma Soft Tissue Sarcoma

U.S. FDA Resources

Further study details as provided by Situs Cancer Research Center:

Primary Outcome Measures:

Efficacy of treatment [ Time Frame: 12-weeks ] [ Designated as safety issue: No ]
Efficacy of treatment will be evaluated at 12-weeks. Efficacy is evaluated using RECIST criteria to determine disease response by CT scan interpretation

Secondary Outcome Measures:

Quality of Life [ Time Frame: 12-weeks ] [ Designated as safety issue: No ]
Quality of life during treatment will be measured using FACT questionnaires.


Estimated Enrollment:	30
Study Start Date:	January 2011
Estimated Study Completion Date:	December 2014
Estimated Primary Completion Date:	July 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Intravenous IVC Intervention Intravenous ascorbic acid, 1.5g/kg at an infusion rate not to exceed 250mg/min.	Drug: Ascorbic acid (vitamin C) Intravenous administration of up to 1.5gm/kg of ascorbic acid, twice weekly for up to 12-weeks. Other Name: Bioniche ascorbic acid, parenteral, 500mg/ml

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.

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01125449

Locations


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

Sponsors and Collaborators

Situs Cancer Research Center

Investigators


Principal Investigator:	G D Murphy, MD	Situs Cancer Research Center
Study Director:	J Bolt, PhD	Situs Cancer Research Center

More Information

Publications:

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.

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.

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. doi: 10.1158/1078-0432.CCR-09-1713. 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. doi: 10.1016/j.freeradbiomed.2009.04.001. Epub 2009 Apr 8.

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.

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.

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. doi: 10.1073/pnas.0804226105. 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.


Responsible Party:	Situs Cancer Research Center
ClinicalTrials.gov Identifier:	NCT01125449 History of Changes
Other Study ID Numbers:	L500HD
Study First Received:	May 16, 2010
Last Updated:	August 25, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Situs Cancer Research Center:


ascorbic acid vitamin C antioxidants vitamins

Additional relevant MeSH terms:


Ascorbic Acid Adenocarcinoma Desmoplastic Small Round Cell Tumor Multiple Myeloma Blood Protein Disorders Carcinoma Cardiovascular Diseases Hematologic Diseases Hemorrhagic Disorders Hemostatic Disorders Immune System Diseases Immunoproliferative Disorders Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type	Neoplasms, Connective and Soft Tissue Neoplasms, Glandular and Epithelial Neoplasms, Plasma Cell Paraproteinemias Sarcoma Vascular Diseases Vitamins Antioxidants Growth Substances Micronutrients Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Protective Agents

ClinicalTrials.gov processed this record on September 25, 2015