N-AcetylCysteine vs. Placebo to Prevent Neurotoxicity Induced by Platinum Containing Chemotherapy (NAC-PNP)

August 22, 2022 updated by: Rijnstate Hospital

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed 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. If peripheral neuropathy can't be measured, neuropathy will be assessed as ototoxicity through measuring audiograms.
  • 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 (Karnofsky 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 study-medication (NAC or placebo) intravenously 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 undergo three electromyographic (EMG) tests, which will normally take place 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. When EMG's can not be measured, audiograms will be used, these audiograms are also part of the routines of treatment, so are not considered an extra burden. Patients will have to fill in Quality of Life questionnaires.
  • Risks: NAC is a well known drug, used for over thirty years, that is well tolerated. 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 preterm arrest of treatment.

Study Type

Interventional

Enrollment (Actual)

69

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Gelderland
      • Arnhem, Gelderland, Netherlands, 6800TA
        • Rijnstate Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)
  • Karnofsky 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 2
Placebo
Drug: Placebo
Placebo once every 3 weeks intravenous saline fluid
Active Comparator: 1
N-Acetylcysteine
Drug: N-Acetylcysteine
N-Acetylcysteine intravenously once every 3 weeks 40 mg/kg
Other Names:
  • Fluimucil

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The occurrence of peripheral neuropathy: with the peripheral neuropathy score (PNP-score) and the electrophysiological measurements. If no EMG is available, then audiometric measurements will be taken into account.
Time Frame: 5 months
5 months

Secondary Outcome Measures

Outcome Measure
Time Frame
haematological abnormalities
Time Frame: 5 months
5 months
creatinine clearance.
Time Frame: 5 months
5 months
liver chemistry abnormalities
Time Frame: 5 months
5 months
Karnofski Performance Score
Time Frame: 5 months
5 months
Quality of life
Time Frame: 5 months
5 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rijnstate Hospital

Investigators

  • Principal Investigator: Idris Bahce, MD, Rijnstate Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2008

Primary Completion (Actual)

July 1, 2017

Study Completion (Actual)

July 1, 2017

Study Registration Dates

First Submitted

March 11, 2008

First Submitted That Met QC Criteria

March 17, 2008

First Posted (Estimate)

March 18, 2008

Study Record Updates

Last Update Posted (Actual)

August 25, 2022

Last Update Submitted That Met QC Criteria

August 22, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LTC-510-100108-Bahce
  • CCMO: NL19614.091.07
  • EudraCT: 2007-002787-95

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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