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
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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
At every clinic visit
Leonard John Hoffer, MD PhD
Faculty of Medicine, McGill University
Canada: Health Canada