Ignite Creation Date:
2024-05-05 @ 7:16 PM
Last Modification Date:
2024-10-26 @ 9:46 AM
Study NCT ID:
NCT00637624
Status:
TERMINATED
Last Update Posted:
2022-08-25
First Post:
2008-03-11
Brief Title:
N-AcetylCysteine vs Placebo to Prevent Neurotoxicity Induced by Platinum Containing Chemotherapy
Sponsor:
Rijnstate Hospital
Organization:
Rijnstate Hospital
Study Overview
Official Title:
A Randomized Double-blind Study of N-AcetylCysteine vs Placebo to Prevent Neurotoxicity Induced by Platinum Containing Chemotherapy in Patients Treated for NonSmall Cell Lung Cancer and Malignant Mesothelioma
Status:
TERMINATED
Status Verified Date:
2022-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Unable to recruit enough patients
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NAC-PNP
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 cant 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 hisher 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 EMGs 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
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 cant 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 hisher 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 EMGs 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| EudraCT 2007-002787-95 | None | None | None |
| CCMO NL1961409107 | None | None | None |