In this study we want to investigate the efficacy of N-acetylcysteine (NAC), which is an anti-oxidant, in the prevention of cisplatin-induced neural toxicity, in patients treated for lung cancer with chemotherapy containing cisplatin...

Date First Received: March 11, 2008

Last Updated: March 17, 2008

Verified by: Rijnstate Hospital, March 2008

Clinical Trial Phase: N/A | Start Date: March 2008

Overall Status: Not yet recruiting

Estimated Enrollment: 50 a

Brief Summary

Official Title: “A Randomized Double-Blind Study of N-AcetylCysteine vs. Placebo to Prevent Neurotoxicity Induced by Platinum Containing Chemotherapy in Patients Treated for (Non)Small Cell Lung Cancer and Malignant Mesothelioma”

Condition Keyword(s):

• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Small Cell Lung
• Mesothelioma

Intervention(s):

• Drug: N-Acetylcysteine
• Drug: Placebo

In this study we want to investigate the efficacy of N-acetylcysteine (NAC), which is an anti-oxidant, in the prevention of cisplatin-induced neural toxicity, in patients treated for lungcancer with chemotherapy containing cisplatin.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Detailed Clinical Trial Description

Background of the study: Cisplatin (CDDP) is a major compound in chemotherapy in patients with non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and malignant mesothelioma. Cisplatin is associated with a number of side-effects, one of which is neurotoxicity. For a number of patients this neurotoxicity is a dose-limiting side-effect. At this point no measures are taken to prevent the occurrence of neurotoxicity during treatment with cisplatin. Recent studies have shown that the association of anti-oxidants to the treatment with cisplatin has a neuroprotective effect without loss of anti-tumour efficacy of cisplatin. One of these anti-oxidants is glutathione (GSH), this is a natural anti-oxidant that is synthesized in all cells, mainly in the liver and the muscles. This GSH plays a central role in the pathophysiology (of efficacy and of side-effects) of cisplatin. We want to investigate the efficacy of N-acetylcysteine (NAC), which serves as a substrate for the synthesis of GSH, in the prevention of cisplatin-induced neurotoxicity.

Objective of the study: The primary objective is to establish the neuroprotective efficacy of NAC against cisplatin-induced neurotoxicity. Mainly the sensory neuronal guidance will be assessed before and after treatment with cisplatin in a group of patients receiving NAC compared to a control-group receiving placebo. - The secondary objectives are establishing the protective effect of NAC regarding other cisplatin-induced side-effects such as haematological pathology (anaemia, leucopenia, thrombopenia, febrile neutropenia), loss of creatinine clearance and occurrence of liver-chemistry abnormalities. Secondary objectives include also establishing the effect on tumour response, clinical performance (Karnofski performance index) and quality of life.

Study design: Monocenter, non-academical teaching hospital, double-blind randomized placebo-controlled study.

Study population: 50 Consecutive patients, who will receive at least 4 cycles of cisplatin in the treatment of NSCLC, SCLC and malignant mesothelioma, will be admitted, irrespective of the disease stage.

Intervention: Patients will be randomized in a placebo-arm and a NAC-arm. They will receive oral study-medication (NAC or placebo) three times a day and they will receive intravenous study-medication every 3 weeks, each time 6 hours after the completion of the cisplatin-infusion.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness

Burdens: Patients will have to take study-medication 3 times daily for the whole period of treatment. The other burden is the electromyographic (EMG) testing, which will normally take place 3 times during the course of the whole treatment, therefore patients will have to visit the hospital to be measured. To minimize this burden, the EMG-measurements will be planned on the same day, the patient has to visit the hospital for reasons regarding his/her regular chemotherapy-treatment. Only surface patch electrodes will be used (no needle electrodes). All other information will be obtained from the patients' files (blood samples, physic evaluations, etc) these are considered to be part of the routines of treatment. Patients will have to fill in Quality of Life questionnaires.

Risks: oral NAC is a well known drug, used for over thirty years, that is well tolerated even if dosed at 600 mg three times daily. For intravenous NAC, allergic reactions have been reported. There is also a theoretical risk, that NAC may reduce anti-tumour efficacy of cisplatin, this risk will be theoretically ruled out by appropriate dosing of NAC. After inclusion of the first 30 patients an interim analysis will be performed regarding the tumour response.

Benefits: NAC will possibly prevent the occurrence of neurotoxicity, improving quality of life. This may, in turn, result in less probability of dose-reductions and of pre-term arrest of treatment.

Outcome Measures for this Clinical Trial

Primary:

• The occurrence of peripheral neuropathy: with the peripheral neuropathy score (PNP-score) and the electrophysiological measurements. 5 months

Secondary:

• haematological abnormalities 5 months
• creatinine clearance. 5 months
• liver chemistry abnormalities 5 months
• Karnofski Performance Score 5 months
• Quality of life 5 months

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• diagnose is histologically or cytologically proven (NSCLC,SCLC), malignant mesothelioma (histologically)
• at least 4 cycles of cisplatin are planned
• adequate renal function (creatinine clearance as calculated by Cockroft-Gault method >
• 60 ml/min)
• Karnofski performance score > 60 %
• written informed consent
• patient must be able to comply with study measurements i.e. hospital visits for EMG and QoL assessments
• age ≥ 18 years

Exclusion Criteria:

• patients with pre-existing neuropathy
• patients not willing to stop earlier prescribed NAC
• patients not willing to stop vitamins E and A above daily advisory dosage
• uncontrolled metastasis in the central or peripheral nervous system

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Rijnstate Hospital

Rijnstate Hospital

Arnhem Gelderland 6800TA Netherlands

Overall Clinical Trial Officials and Contacts

Idris Bahce, MD Principal Investigator Rijnstate Hospital

Overall Contact: Idris Bahce, M.D. +31263788888 IBahce@alysis.nl

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00637624

Study ID Number: LTC-510-100108-Bahce

ClinicalTrials.gov Identifier: NCT00637624

Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial