The Use of Glutathione (GSH) for Prevention of Paclitaxel/Carboplatin (TAXOL/CBDCA) Induced Peripheral Neuropathy: A Phase III Randomized, Double-Blind Placebo Controlled Study
The Use of Glutathione (GSH) for Prevention of Paclitaxel/Carboplatin (TAXOL/CBDCA) Induced Peripheral Neuropathy: A Phase III Randomized, Double-Blind Placebo Controlled Study
This randomized phase III trial is studying glutathione to see how well it works in preventing peripheral neuropathy caused by paclitaxel and carboplatin in patients with ovarian cancer, fallopian tube cancer, and/or primary peritoneal cancer. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemoprotective drugs, such as glutathione, may help prevent peripheral neuropathy caused by paclitaxel and carboplatin. It is not yet known whether glutathione is more effective than a placebo in preventing peripheral neuropathy.
PRIMARY OBJECTIVES:
I. To compare TAXOL (paclitaxel)/carboplatin (CBDCA) induced peripheral neuropathy as measured by European Organization for Research and Treatment of Cancer (EORTC)- Quality of Life (QOL)-chemotherapy induced peripheral neuropathy 20 (CIPN20) between glutathione (GSH) and placebo arms.
SECONDARY OBJECTIVES:
I. To compare the incidences of grade 2+ and grade 3+ TAXOL/CBDCA induced peripheral neuropathy measured by Common Terminology Criteria for Adverse Events (CTCAE) neuropathy scale between GSH and placebo arms.
II. To compare the time to onset of grade 2+ and grade 3+ TAXOL/CBDCA induced peripheral neuropathy between GSH and placebo arms, measured by CTCAE neuropathy scale.
III. To compare the proportion of patients requiring chemotherapy dose reductions secondary to TAXOL/CBDCA induced peripheral neuropathy between GSH and placebo arms.
IV. To compare the proportion of patients stopping TAXOL/CBDCA secondary to peripheral neuropathy between GSH and placebo arms.
V. To assess the toxicity profile of GSH in this situation. VI. To evaluate whether GSH influences the anti-tumor activity of TAXOL/CBDCA. VII. To evaluate patient quality of life (QOL) measured by Functional Assessment of Cancer Therapy-Ovarian (FACT-O) (ovarian/fallopian tube/primary peritoneal cancer patients only) and patient daily symptom questionnaires over time between GSH and placebo arms.
TERTIARY:
I. To explore the association of genetic variations in genes involved in taxane/platinum metabolism with incidence of grade 2+ TAXOL/CBDCA induced peripheral neuropathy.
II. As part of ongoing research for North Central Cancer Treatment Group (NCCTG) studies, we are banking blood products for future studies.
OUTLINE:
Patients are stratified according to baseline neuropathy (none vs grade 1), 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), and cancer type (ovarian/fallopian tube/primary peritoneal cancers vs lung cancer vs other). Patients are randomized to 1 of 2 treatment arms. Patients are grouped based on, Planned paclitaxel dose cycle length (Weekly vs. every 3 weeks vs. every 4 weeks). The stratification factors listed include demographic, prognostic factors and medication that can potentially impact the primary or secondary outcomes, so they need to be distributed evenly among the two arms. The 18 level combinations involved in these four stratification factors are within the maximum recommended of one half of the group sample size for the study.
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 intravenously (IV) over 15 minutes, paclitaxel* IV over 1 or 3 hours depending on planned dose cycle length and carboplatin IV over 30 minutes.
ARM II: Patients receive placebo IV over 15 minutes, paclitaxel* IV over 1 or 3 hours depending on planned dose cycle length and carboplatin IV over 30 minutes.
NOTE: *Alternatively, patients may receive paclitaxel IV over 1 hour and glutathione/placebo IV over 15 minutes weekly and carboplatin every 21 days for 12 weeks.
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 every 3 months for 1 year.
Inclusion Criteria:
Exclusion Criteria:
Pre-existing history of peripheral neuropathy > grade 1 (National Cancer Institute [NCI] CTCAE version [v] 4.0) due to any cause (e.g., chemotherapy, diabetes, alcohol, toxin, or heredity)
Other medical conditions, which in the opinion of the treating physician/allied health professional would make this protocol unreasonably hazardous for the patient
Any of the following:
Prior TAXOL and/or CBDCA chemotherapy treatment (other than the current treatment regimen)
Concurrent use of any agent being used specifically to prevent or treat neuropathy, including but not limited to the following:
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