Trial of Chemotherapy Plus Intravenous Vitamin C in Patients With Advanced Cancer for Whom Chemotherapy Alone is Only Marginally Effective

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
John Hoffer, Jewish General Hospital
ClinicalTrials.gov Identifier:
NCT01050621
First received: January 11, 2010
Last updated: June 20, 2013
Last verified: June 2013
  Purpose

Concurrent administration of intravenous vitamin C (ascorbic acid, 1.5 g/kg, infused two or three times weekly) together with certain cytotoxic chemotherapy regimens could prove to be an effective treatment for some patients with advanced malignancies for whom existing chemotherapy is usually ineffective. The primary objectives of this study are to identify a tolerable and safe dose of intravenous vitamin C when administered during cytotoxic chemotherapy while attempting to empirically identify specific vitamin C-chemotherapy regimens for which the clinical response is unusually favorable after a minimum of 2 months of therapy, as determined by CT scan and biomarkers, when appropriate.


Condition Intervention Phase
Cancer
Dietary Supplement: vitamin C (ascorbic acid)
Phase 1
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 I - II Clinical Trial of Combination Conventional Cytotoxic Chemotherapy and Intravenous Vitamin C in Patients With Advanced Cancer or Hematologic Malignancy for Whom Cytotoxic Chemotherapy Alone is Only Marginally Effective

Resource links provided by NLM:


Further study details as provided by Jewish General Hospital:

Primary Outcome Measures:
  • Safety and tolerability of IV ascorbic acid (IVAA) in target dose of 1500 mg/kg supplementing cytotoxic chemotherapeutic drugs. Standard adverse effect criteria will be used. [ Time Frame: At every clinic visit ] [ Designated as safety issue: Yes ]
  • Observe for qualitative indicators that IV ascorbic acid mitigates chemotherapy adverse effects [ Time Frame: Every treatment cycle ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To monitor for disease arrest or response (RECIST criteria) in a population in which arrest or response is unusual or rare [ Time Frame: CT assessment every 2 months ] [ Designated as safety issue: No ]
  • Quality of life assessment using FACT B and POMS R [ Time Frame: every month ] [ Designated as safety issue: No ]
  • Measure the effect of chemotherapy on pharmacokinetics of intravenous ascorbic acid [ Time Frame: Before and 5 days following first chemotherapy ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: January 2010
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Dietary Supplement: vitamin C (ascorbic acid)
    ascorbic acid 1.5 g/kg body weight infused over 90 to 120 minutes two or three times weekly concurrent with standard cytotoxic chemotherapy individually selected for each patient by the treating oncologist on the basis of best current clinical practice
Detailed Description:

Cytotoxic chemotherapy is relatively ineffective for a large proportion of common cancers. Combining redox active molecules with certain chemotherapy regimens could increase their anti-cancer activity or protect host tissues from toxicity with no loss of anti-cancer activity. Research in this area has been advocated by cancer organizations, but previous clinical trials of combination chemotherapy and antioxidant therapy been small, poorly designed, and unsystematic. Appropriate study of this treatment concept requires a systematic, meticulous empirical approach similar to the one used in conventional cytotoxic drug discovery. This is a Phase I-II study designed to identify promising chemotherapy-antioxidant protocols and determine their acceptability and limiting toxicity in patients with relentlessly progressive cancers for which conventional chemotherapy is clinically indicated but is known to be minimally or marginally effective.

The tolerable dose of intravenous ascorbic acid (IVAA) for cancer patients with normal renal function not receiving chemotherapy is 1.5 g/kg per 90 to 120 minute infusion (Hoffer et al, Ann Oncol 2008;19:1969-1974). Side effects are minimal to non-existent. In this dose-escalating study the IVAA will be 0.9 g/kg per infusion for the first chemotherapy cycle, increasing to 1.5 g/kg per infusion in subsequent cycles, for the first 3 participants. If well tolerated as expected, the initial dose will be 1.5 g/kg per infusion for subsequent participants. Infusions will take place 2 or 3 times per week, bracketing the days of chemotherapy. Standard tolerance and adverse effect criteria will be used. Therapy will continue for a minimum of 2 months, and continue further in the event of disease stabilization or response, as determined from CT scan and biomarkers, with evaluations continuing every 2 months.

  Eligibility

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

Inclusion Criteria:

  • must be a resident of Quebec, Canada
  • documented advanced or metastatic cancer or hematologic malignancy in adults over age 18, with measurable disease
  • adequate bone marrow, hepatic, renal and cardiac function so as to permit conventional chemotherapy
  • no current calcium oxalate nephrolithiasis with the potential to reduce urinary flow
  • life expectancy at least 8 weeks.

Exclusion Criteria:

  • glucose-6-phosphate dehydrogenase deficiency
  • cancers for which existing chemotherapy offers more than a 33% likelihood of a clinically meaningful response
  • serum creatinine greater than 175 micromol/L
  • serious GI diseases
  • infections
  • recent major surgery
  • dementia
  • altered mental status or other condition that would preclude chemotherapy, including poor functional status.
  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: NCT01050621

Locations
Canada, Quebec
Clinical Research Unit, Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
Sponsors and Collaborators
Jewish General Hospital
Investigators
Principal Investigator: Leonard John Hoffer, MD PhD Faculty of Medicine, McGill University
  More Information

No publications provided

Responsible Party: John Hoffer, Physician, Jewish General Hospital
ClinicalTrials.gov Identifier: NCT01050621     History of Changes
Other Study ID Numbers: VITC-003
Study First Received: January 11, 2010
Last Updated: June 20, 2013
Health Authority: Canada: Health Canada

Keywords provided by Jewish General Hospital:
ascorbic acid
vitamin C
antioxidants
redox therapy
cytotoxic chemotherapy

Additional relevant MeSH terms:
Ascorbic Acid
Vitamins
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on July 28, 2014