Glutathione in Preventing Peripheral Neuropathy Caused by Paclitaxel and Carboplatin in Patients With Ovarian Cancer, Fallopian Tube Cancer, and/or Primary Peritoneal Cancer

OBJECTIVES:

Primary

- To compare paclitaxel/carboplatin (PC)-induced (PCI) peripheral neuropathy (PN) as
measured by EORTC-QLQ-CIPN20 between patients with ovarian cancer and/or primary
peritoneal carcinoma treated with glutathione vs placebo.

Secondary

- To compare the incidences of grade 2+ and grade 3+ PCI PN as measured by CTCAE
neuropathy scale between the glutathione and placebo arms.

- To compare the time to onset of grade 2+ and grade 3+ PCI PN between the treatment arms
as measured by CTCAE neuropathy scale.

- To compare the proportion of patients requiring chemotherapy dose reductions secondary
to PCI PN between the treatment arms.

- To compare the proportion of patients stopping PC secondary to peripheral neuropathy
between the arms.

- To assess the toxicity profile of glutathione in this situation.

- To evaluate whether glutathione influences the antitumor activity of PC.

- To evaluate patient quality of life as measured by FACT-O and patient daily-symptom
questionnaires over time between the treatment arms.

Tertiary (exploratory)

- To explore the association of genetic variations in genes involved in taxane/platinum
metabolism with the incidence of grade 2+ PCI PN.

- To bank blood products for future studies.

OUTLINE: Patients are stratified according to baseline neuropathy (none vs grade 1), age (≤
50 years vs > 50 years), debulked status (no gross residual disease [no clinically apparent
residual lesions at the completion of primary surgery] vs optimal [largest residual lesion <
1 cm at primary surgery] vs sub-optimally debulked [residual lesion > 1 cm] or not operated
upon), concurrent use of bevacizumab (yes vs no), paclitaxel planned dose (weekly vs every 3
weeks), and diabetes requiring insulin or oral hypoglycemic medications (yes vs no).
Patients are randomized to 1 of 2 treatment arms.

Ideally, patients begin receiving glutathione before their first dose of chemotherapy, but
must begin glutathione before their second dose of chemotherapy.

- Arm I: Patients receive glutathione IV over 15 minutes, paclitaxel IV over 3 hours, and
carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses
in the absence of disease progression or unacceptable toxicity.

- Arm II: Patients receive placebo IV over 15 minutes, paclitaxel IV over 3 hours, and
carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses
in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for pharmacogenomic and other biomarker analyses.
Patients complete questionnaires periodically, including quality-of-life assessments.

After completion of study treatment, patients are followed up monthly for 1 year and then
annually for 5 years.