Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: 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.

PURPOSE: 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.

Further Study Information

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 21-28 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.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of stage III/IV ovarian cancer, fallopian tube cancer, and/or primary peritoneal carcinoma

• Scheduled to undergo treatment with paclitaxel at 175 mg/m^2 and carboplatin at area under the curve = 6 every 21 days for 6 courses with or without bevacizumab

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy ≥ 6 months

• WBC ≥ 3,400/mm^3

• ANC ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin > 10.0 g/dL

• Creatinine ≤ 1.5 times upper limit of normal

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Able to complete English language questionnaire(s) alone or with assistance

• Willing to provide blood specimens as required by the study

• No pre-existing history of peripheral neuropathy > grade 1 (NCI CTCAE v4.0) due to any cause (e.g., chemotherapy, diabetes, alcohol, toxin, or heredity)

• No other medical conditions that, in the opinion of the treating physician/allied health professional, would make this study unreasonably hazardous for the patient

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior paclitaxel or carboplatin other than the current treatment regimen

• No other concurrent treatment for the prevention of peripheral neuropathy, including prescription and over-the-counter or herbal therapies

Trial Contact Information

Trial Lead Organizations/Sponsors

North Central Cancer Treatment Group

Charles L. Loprinzi

Study Chair

U.S.A.
Minnesota
	Rochester
	North Central Cancer Treatment Group
		Charles L. Loprinzi	Ph: 507-284-1623
			Email: cloprinzi@mayo.edu

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00979082
Information obtained from ClinicalTrials.gov on February 21, 2013

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