Ignite Creation Date:
2024-05-06 @ 10:45 AM
Last Modification Date:
2024-10-26 @ 12:35 PM
Study NCT ID:
NCT03344328
Status:
COMPLETED
Last Update Posted:
2020-11-12
First Post:
2017-10-18
Brief Title:
Prevalence Intensity and Consequences of Bortezomib-induced Neuropathic Disorders
Sponsor:
University Hospital Clermont-Ferrand
Organization:
University Hospital Clermont-Ferrand
Study Overview
Official Title:
Evaluation of the Prevalence Intensity and Consequences of Bortezomib-induced Neuropathic Disorders Monocentric Observational and Cross-sectional Study
Status:
COMPLETED
Status Verified Date:
2019-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PREVIB
Brief Summary:
Cancer-induced peripheral neuropathies CIPN remain a real problem in oncology Balayssac et al 2011 These CIPN are induced by certain classes of anticancer drugs such as taxanes paclitaxel and docetaxel platinum salts cisplatin and oxaliplatin alkaloids of Madagascar periwinkle vincristine bortezomib thalidomide and eribulin Balayssac et al 2011 Vahdat et al 2013 These CIPN essentially translate into sensory disorders such as paresthesia dysesthetics or numbness More rarely these CIPN may be associated with motor or vegetative disorders Balayssac et al 2011 According to the recent meta-analysis by Hershman et al no treatment can be proposed as a gold standard for preventing or treating CIPN Hershman et al 2014 As a result oncologists reduce or stop doses of neurotoxic anticancer drugs because patients with CIPN have a marked deterioration in quality of life and co-morbidities such as anxiety depression and sleep disorders Hong et al 2014 Mols et al 2014 Therefore understanding the pathophysiology of CIPN is essential to propose new therapeutic strategies
Among neurotoxic anticancer drugs bortezomib remains relatively little studied in terms of pathophysiology compared to platinum salts or taxanes while the neurotoxicity of bortezomib remains a limiting factor in treatment Since 2012 the FDA and EMA have validated the administration of bortezomib subcutaneously instead of intravenously in order to limit the neurotoxicity of bortezomib Minarik et al 2015 Indeed a large study N222 reported that subcutaneous administration of bortezomib allowed the same therapeutic efficacy to be maintained while improving the safety profile and in particular limiting peripheral neuropathies CIPN all grades 38 vs 53 p0044 grade 2 24 vs 41 p0012 and grade 3 6 vs 16 p0026 However a recent retrospective study N446 reports that the prevalence of bortezomib-induced peripheral neuropathies after subcutaneous administration remains relatively high all grade 41 grade 2 18 grade 3 4 and above all that this prevalence is not different between subcutaneous and intravenous routes Minarik et al 2015
Among neurotoxic anticancer drugs bortezomib remains relatively little studied in terms of pathophysiology compared to platinum salts or taxanes while the neurotoxicity of bortezomib remains a limiting factor in treatment Since 2012 the FDA and EMA have validated the administration of bortezomib subcutaneously instead of intravenously in order to limit the neurotoxicity of bortezomib Minarik et al 2015 Indeed a large study N222 reported that subcutaneous administration of bortezomib allowed the same therapeutic efficacy to be maintained while improving the safety profile and in particular limiting peripheral neuropathies CIPN all grades 38 vs 53 p0044 grade 2 24 vs 41 p0012 and grade 3 6 vs 16 p0026 However a recent retrospective study N446 reports that the prevalence of bortezomib-induced peripheral neuropathies after subcutaneous administration remains relatively high all grade 41 grade 2 18 grade 3 4 and above all that this prevalence is not different between subcutaneous and intravenous routes Minarik et al 2015
Detailed Description:
Only 2 studies evaluated quantitatively and qualitatively the sensitivity disorders in patients with bortezomib-induced peripheral neuropathy by intravenous Boyette-Davis et al 2011 Cata et al 2007 In these 2 studies the patients presented a distribution of the sensitive disorders characteristic of the so-called stocking-glove distribution of the CIPN affecting the distal extremities of the limbs A quantification of the sensory thresholds QST was carried out and revealed a number of sensitive anomalies Neuropathic patients suffer from deficits in tactile sensitivity and disorders of thermal sensitivity In Cata et al study patients showed hypersensitivity to painful cold CIPN patients vs healthy controls 1042C vs 31C p005 hot perception deficit CIPN patients vs healthy controls 40214C vs 37074C p005 and a painful hot sensitivity deficit However the cold sensory disorders would be more inconstant because in neuropathic patients suffering from bortezomib-induced peripheral neuropathy another study by the same team found only warm tactile and thermal sensory anomalies but did not reveal a cold perception anomaly Boyette-Davis et al 2011 Finally a few rare cases of bortezomib-induced hearing impairment have been described in the literature Chim and Wong 2008 Engelhardt et al 2005 This ototoxicity is thought to be linked to an alteration in the functioning of peroxisomes Lee et al 2015
No studies have actually evaluated the long-term prevalence of bortezomib-induced neuropathy The only studies with long-term follow-up have carried out a cumulative assessment over 22 months Pantani et al 2014 32 months Dimopoulos et al 2013 and 60 months Wang et al 2016 of the therapeutic response and adverse reactions induced by bortezomib No studies dedicated to neurological adverse events have been conducted in the long term Thus the prevalence duration intensity and reversibility of bortezomib-induced neuropathy are poorly known in the long term more than 5 years On the other hand a measurement tool such as the QLQ-CIPN20 questionnaire EORTC evaluating the intensity of sensory motor and vegetative disorders associated with CIPN a questionnaire presented as the most specific tool in the evaluation of CIPN Lavoie Smith et al 2013 Postma et al 2005 has never been tested in this patient population
This study project aims to provide precise knowledge on the prevalence intensity and consequences of bortezomib-induced neuropathy in the short 2016-2014 and medium 2014-2012 term after subcutaneous injection and in the long term 2012-2008 after intravenous injection knowing that at the Clermont-Ferrand University Hospital the route of administration of bortezomib was intravenous Retreat to at least 9 years of age could provide information on the kinetics of onset and disappearance of neuropathy after chemotherapy treatments data unknown in the literature to date Finally these data acquired in a French context relating to bortezomib-induced neuropathy may be used in future studies evaluating new intervention strategies to prevent andor treat bortezomib-induced neuropathy
This observational study will combine retrospective treatment data from the CHIMIO chemotherapy prescribing software with data obtained from patients by answering questionnaires
Patients will be identified from the CHIMIO chemotherapy prescription software database The algorithm computer query will identify all patients who received bortezomib-based chemotherapy for the multiple myeloma indication between 2008 and 2016 All the questionnaires used are validated in the scientific literature
No studies have actually evaluated the long-term prevalence of bortezomib-induced neuropathy The only studies with long-term follow-up have carried out a cumulative assessment over 22 months Pantani et al 2014 32 months Dimopoulos et al 2013 and 60 months Wang et al 2016 of the therapeutic response and adverse reactions induced by bortezomib No studies dedicated to neurological adverse events have been conducted in the long term Thus the prevalence duration intensity and reversibility of bortezomib-induced neuropathy are poorly known in the long term more than 5 years On the other hand a measurement tool such as the QLQ-CIPN20 questionnaire EORTC evaluating the intensity of sensory motor and vegetative disorders associated with CIPN a questionnaire presented as the most specific tool in the evaluation of CIPN Lavoie Smith et al 2013 Postma et al 2005 has never been tested in this patient population
This study project aims to provide precise knowledge on the prevalence intensity and consequences of bortezomib-induced neuropathy in the short 2016-2014 and medium 2014-2012 term after subcutaneous injection and in the long term 2012-2008 after intravenous injection knowing that at the Clermont-Ferrand University Hospital the route of administration of bortezomib was intravenous Retreat to at least 9 years of age could provide information on the kinetics of onset and disappearance of neuropathy after chemotherapy treatments data unknown in the literature to date Finally these data acquired in a French context relating to bortezomib-induced neuropathy may be used in future studies evaluating new intervention strategies to prevent andor treat bortezomib-induced neuropathy
This observational study will combine retrospective treatment data from the CHIMIO chemotherapy prescribing software with data obtained from patients by answering questionnaires
Patients will be identified from the CHIMIO chemotherapy prescription software database The algorithm computer query will identify all patients who received bortezomib-based chemotherapy for the multiple myeloma indication between 2008 and 2016 All the questionnaires used are validated in the scientific literature
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None