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

Pain Clinical Trial

Official title: The Use of Glutathione (GSH) for Prevention of Paclitaxel/Carboplatin (TAXOL/CBDCA) Induced Peripheral Neuropathy: A Phase III Randomized, Double-Blind Placebo Controlled Study

Status Completed

Clinical Trial Summary

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.

Clinical Trial Description

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), 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 intravenously (IV) over 15 minutes, paclitaxel* IV over 3 hours, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21-28 days for at least 12 weeks 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 as in arm I.

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. ;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Chemotherapeutic Agent Toxicity
• Fallopian Tube Neoplasms
• Neuropathy
• Neurotoxicity Syndrome
• Neurotoxicity Syndromes
• Ovarian Neoplasms
• Pain
• Peripheral Nervous System Diseases
• Peritoneal Neoplasms
• Stage IIIA Fallopian Tube Cancer
• Stage IIIA Ovarian Cancer
• Stage IIIA Primary Peritoneal Cancer
• Stage IIIB Fallopian Tube Cancer
• Stage IIIB Ovarian Cancer
• Stage IIIB Primary Peritoneal Cancer
• Stage IIIC Fallopian Tube Cancer
• Stage IIIC Ovarian Cancer
• Stage IIIC Primary Peritoneal Cancer
• Stage IV Fallopian Tube Cancer
• Stage IV Ovarian Cancer
• Stage IV Primary Peritoneal Cancer

• NCT number: NCT02311907
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Completed
• Phase: Phase 3
• Start date: December 2009
• Completion date: August 2012