Study of High Dose Intravenous (IV) Ascorbic Acid in Measurable Solid Tumor Disease
Primary Purpose
Sarcoma, Adenocarcinoma, Carcinoma
Status
Suspended
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ascorbic acid (vitamin C)
Sponsored by
About this trial
This is an interventional treatment trial for Sarcoma focused on measuring ascorbic acid, vitamin C, antioxidants, vitamins
Eligibility 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
Sites / Locations
- Situs Cancer Research Center
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Intravenous IVC Intervention
Arm Description
Intravenous ascorbic acid, 1.5g/kg at an infusion rate not to exceed 250mg/min.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Quality of Life
Quality of life during treatment will be measured using FACT questionnaires.
Full Information
NCT ID
NCT01125449
First Posted
May 16, 2010
Last Updated
August 25, 2012
Sponsor
Situs Cancer Research Center
1. Study Identification
Unique Protocol Identification Number
NCT01125449
Brief Title
Study of High Dose Intravenous (IV) Ascorbic Acid in Measurable Solid Tumor Disease
Official Title
Phase 2 Study of High Dose Ascorbic Acid in Solid Tumor Disease
Study Type
Interventional
2. Study Status
Record Verification Date
August 2012
Overall Recruitment Status
Suspended
Why Stopped
Awaiting response from FDA as to status of parenteral ascorbic acid manufactured by Bioniche (Ireland).
Study Start Date
January 2011 (undefined)
Primary Completion Date
July 2014 (Anticipated)
Study Completion Date
December 2014 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Situs Cancer Research Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma, Adenocarcinoma, Carcinoma, Multiple Myeloma, Desmoplastic Small Round Cell Tumor
Keywords
ascorbic acid, vitamin C, antioxidants, vitamins
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intravenous IVC Intervention
Arm Type
Other
Arm Description
Intravenous ascorbic acid, 1.5g/kg at an infusion rate not to exceed 250mg/min.
Intervention Type
Drug
Intervention Name(s)
Ascorbic acid (vitamin C)
Other Intervention Name(s)
Bioniche ascorbic acid, parenteral, 500mg/ml
Intervention Description
Intravenous administration of up to 1.5gm/kg of ascorbic acid, twice weekly for up to 12-weeks.
Primary Outcome Measure Information:
Title
Efficacy of treatment
Description
Efficacy of treatment will be evaluated at 12-weeks. Efficacy is evaluated using RECIST criteria to determine disease response by CT scan interpretation
Time Frame
12-weeks
Secondary Outcome Measure Information:
Title
Quality of Life
Description
Quality of life during treatment will be measured using FACT questionnaires.
Time Frame
12-weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
G D Murphy, MD
Organizational Affiliation
Situs Cancer Research Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
J Bolt, PhD
Organizational Affiliation
Situs Cancer Research Center
Official's Role
Study Director
Facility Information:
Facility Name
Situs Cancer Research Center
City
Rogers
State/Province
Arkansas
ZIP/Postal Code
72756
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
18789157
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.
Results Reference
background
PubMed Identifier
18450228
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.
Results Reference
background
PubMed Identifier
17519294
Citation
Duconge J, Miranda-Massari JR, Gonzalez 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. doi: 10.1345/aph.1H654. Epub 2007 May 22. No abstract available.
Results Reference
background
PubMed Identifier
16570523
Citation
Riordan HD, Casciari JJ, Gonzalez 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.
Results Reference
background
PubMed Identifier
20068072
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.
Results Reference
background
PubMed Identifier
19361554
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. No abstract available.
Results Reference
background
PubMed Identifier
19154961
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.
Results Reference
background
PubMed Identifier
18544557
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.
Results Reference
background
PubMed Identifier
17502596
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. doi: 10.1073/pnas.0702854104. Epub 2007 May 14.
Results Reference
background
PubMed Identifier
16157892
Citation
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. doi: 10.1073/pnas.0506390102. Epub 2005 Sep 12.
Results Reference
background
PubMed Identifier
18678913
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.
Results Reference
background
PubMed Identifier
19414313
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.
Results Reference
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Study of High Dose Intravenous (IV) Ascorbic Acid in Measurable Solid Tumor Disease
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