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

Primary Purpose

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

Status
Terminated
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
N-Acetylcysteine
Placebo
Sponsored by
Rijnstate Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Carcinoma, Non-Small-Cell Lung focused on measuring Acetylcysteine, Cisplatin, Neuropathy, Antioxidants

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Rijnstate Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

1

2

Arm Description

N-Acetylcysteine

Placebo

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
March 11, 2008
Last Updated
August 22, 2022
Sponsor
Rijnstate Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT00637624
Brief Title
N-AcetylCysteine vs. Placebo to Prevent Neurotoxicity Induced by Platinum Containing Chemotherapy
Acronym
NAC-PNP
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Terminated
Why Stopped
Unable to recruit enough patients
Study Start Date
March 2008 (undefined)
Primary Completion Date
July 2017 (Actual)
Study Completion Date
July 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rijnstate Hospital

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Non-Small-Cell Lung, Carcinoma, Small Cell Lung, Mesothelioma
Keywords
Acetylcysteine, Cisplatin, Neuropathy, Antioxidants

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
69 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
N-Acetylcysteine
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
N-Acetylcysteine
Other Intervention Name(s)
Fluimucil
Intervention Description
N-Acetylcysteine intravenously once every 3 weeks 40 mg/kg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo once every 3 weeks intravenous saline fluid
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
haematological abnormalities
Time Frame
5 months
Title
creatinine clearance.
Time Frame
5 months
Title
liver chemistry abnormalities
Time Frame
5 months
Title
Karnofski Performance Score
Time Frame
5 months
Title
Quality of life
Time Frame
5 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Idris Bahce, MD
Organizational Affiliation
Rijnstate Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rijnstate Hospital
City
Arnhem
State/Province
Gelderland
ZIP/Postal Code
6800TA
Country
Netherlands

12. IPD Sharing Statement

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N-AcetylCysteine vs. Placebo to Prevent Neurotoxicity Induced by Platinum Containing Chemotherapy

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