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

Jewish General Hospital

Status and phase

Completed

Phase 2

Phase 1

Conditions

Cancer

Treatments

Dietary Supplement: vitamin C (ascorbic acid)

Study type

Interventional

Funder types

Other

Identifiers

NCT01050621

VITC-003

Details and patient eligibility

About

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.

Full 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.

Enrollment

14 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.