Vitamin C as an Anti-cancer Drug

NCT ID: NCT01080352

Last Updated: 2015-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2015-03-31

Brief Summary

Can high dose, intravenous Vitamin C prolong life for patients with metastatic prostate cancer?

Prostate cancer is the most common cancer (excluding skin cancer) in men in Denmark and the Unites States. When metastatic disease is present cure is no longer possible. The main treatment at this stage is castration, either surgical or medical, ending the patients testosterone production and causing a temporary regression in disease activity.

Eventually, the cancer will progress, usually within 2 years from the castration, with a more aggressive course and a survival of 2-3 years.

The current treatment option for the patients, who have undergone castration and have disease progression, is chemotherapy with only limited gains in quality of life and survival.

This clinical study is a phase 2 study to evaluate the effects of high dose intravenous vitamin c in subjects with early castration resistant prostate cancer.

Primary endpoint:

• Prostate specific antigen (PSA) changes after 12 to 20 weekly vitamin c infusions

Secondary endpoints:

• Bone metastases changes after 12 to 20 weekly vitamin c infusions
• Changes in bone specific alkaline phosphates, oxidative DNA-damage, PINP, NTX after 12 to 20 weekly vitamin c infusions
• RNA-expression changes in prostatic tumor tissue after 12 to 20 weekly vitamin c infusions
• RNA-expression changes in lymphocytes after 12 to 20 weekly vitamin c infusions

Tertiary endpoints:

• Pharmacokinetics of vitamin c in the elderly cancer patients

Methods and material:

• 80 subjects are included (efficacy evaluation when 20 subjects have been evaluated for extension arm)
• Each subject receives a weekly infusion of 60 grams vitamin c (in the form of ascorbate) for 12 to 20 weeks

Detailed Description

Vitamin C for palliative treatment:

Intravenous vitamin C has been used since the 1970's for terminally ill cancer patients claiming big increases in survival time. The efficacy of the drug is questioned and no randomized, controlled trial of Vitamin C's efficacy on cancer patients survival has been made.

Recent results from in vitro and xenograft studies in mice has shown some promise for vitamin c as a cytotoxic agent against cancer cells.

The following parameters are recorded for baseline:

• Biomarkers (PSA, bALP, NTX, PINP)
• Routine blood work (hgb, creatinine, p-vitamin c etc.)
• Radio nucleotide bone scintigraphy
• Prostate biopsies for later microarray (Affymetrix ST1.0)
• Urine samples 8-oxo-guanine(for oxidative DNA-damage measurements)

These parameters are repeated after treatment, usually after 12 to 26 weeks after the first vitamin c infusion.

Conditions

Prostatic Neoplasms

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vitamin C treatment

Each subjects receive 12 weeks of 1 weekly treatment with intravenous vitamin c.

5grams are given at week 1, 30 grams at week 2 and 60 grams at week 3-12. If eligibility criteria are met the subject may continue with 1 weekly vitamin c treatment of 60 grams at week 13-20.

Group Type: EXPERIMENTAL

Ascorbic Acid (Vitamin C)

Intervention Type: DRUG

60grams of ascorbate given intravenous infusion in 1000ml sterile water.

Interventions

Ascorbic Acid (Vitamin C)

60grams of ascorbate given intravenous infusion in 1000ml sterile water.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Castration resistant metastatic prostate cancer (bony or visceral metastases)
• Gleason sum > 6
• PSA > 10 ng/ml
• ECOG < 3
• Prior orchidectomy or LHRH antagonist/agonist treatment
• Must give informed content

Exclusion Criteria

• Synchronous active cancer (skin cancer excluded)
• Prior chemotherapy
• History of oxalate renal stones
• Glucose-6-phosphate dehydrogenase deficiency
• Impaired renal function (creatinine > 200micromoles/L
• Haemochromatosis
• Cardiac disease (NYHA > 2, CSS > 2, recent AMI (less than 6 months)
• Recent major surgery (less than 4 weeks before inclusion and more than 2 days of admittance time)
• Prior intended curative treatment of prostate cancer

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Rigshospitalet, Denmark

OTHER

Sponsor Role: collaborator

University of Copenhagen

OTHER

Sponsor Role: collaborator

Copenhagen University Hospital at Herlev

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kari J Mikines, MD, DsMC

Role: PRINCIPAL_INVESTIGATOR

Copenhagen University Hospital at Herlev

Locations

Departmen of Urology, Copenhagen University Hospital at Herlev

Herlev, DK, Denmark

Countries

Denmark

References

Nielsen TK, Hojgaard M, Andersen JT, Jorgensen NR, Zerahn B, Kristensen B, Henriksen T, Lykkesfeldt J, Mikines KJ, Poulsen HE. Weekly ascorbic acid infusion in castration-resistant prostate cancer patients: a single-arm phase II trial. Transl Androl Urol. 2017 Jun;6(3):517-528. doi: 10.21037/tau.2017.04.42.

Reference Type: DERIVED

PMID: 28725594 (View on PubMed)

Nielsen TK, Hojgaard M, Andersen JT, Poulsen HE, Lykkesfeldt J, Mikines KJ. Elimination of ascorbic acid after high-dose infusion in prostate cancer patients: a pharmacokinetic evaluation. Basic Clin Pharmacol Toxicol. 2015 Apr;116(4):343-8. doi: 10.1111/bcpt.12323. Epub 2014 Oct 7.

Reference Type: DERIVED

PMID: 25220574 (View on PubMed)

Related Links

http://www.herlevhospital.dk/menu/Afdelinger/Urologisk_Afdeling_H/Forskning/Vitamin+C/

Participant information (in Danish)

Other Identifiers

2008-008692-33

Identifier Type: -

Identifier Source: org_study_id