Clinical trial NCT02311907
Conditions: Chemotherapeutic Agent Toxicity Neuropathy Neurotoxicity Syndrome Pain 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
Sponsor: Alliance for Clinical Trials in Oncology
Start date: 2009-12-01; Completion date: 2012-08-01
Enrollment: 195 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Detailed 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), 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.

Arms: arm 1: 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 2: 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.
Interventions: intervention 1: Carboplatin intervention 2: Glutathione intervention 3: Laboratory Biomarker Analysis intervention 4: Paclitaxel intervention 5: Placebo intervention 6: Quality-of-Life Assessment
Intervention descriptions: intervention 1: Given IV, over 30 minutes per planned chemotherapy regimen intervention 2: Given IV, over 15 minutes, immediately before chemotherapy administration intervention 3: Correlative studies intervention 4: Given IV, over 1 or 3 hours, per planned chemotherapy regimen intervention 5: Given IV intervention 6: Ancillary studies

Protocol documents: