Neurotoxic Effect of Bortezomib Treatment in Patient With Myeloma Multiple (SENSIB)

June 28, 2019 updated by: University Hospital, Clermont-Ferrand

Assessment of Sensory Disorders Associated With Peripheral Neuropathy Induced by Bortezomib: Prospective Comparative Study

Chemotherapy-induced peripheral neuropathies (CIPN) remain a problem in oncology because no "gold standard" treatment exists to prevent or treat the CIPN. Therefore, oncologists reduce or stop the chemotherapy doses to limit degradation of the quality of life of patients with CIPN. Bortezomib is relatively understudied while neurotoxicity remains a limiting factor for treatment. Since 2012, the FDA and the EMA validated by the administration of bortezomib subcutaneously (SC) instead of intravenous (IV) in order to limit neurotoxicity.

However, a retrospective study reported that the prevalence of neuropathy induced by bortezomib after SC administration remains high and equivalent to IV route. No studies have quantitatively and qualitatively evaluated the sensory disorders in peripheral neuropathies induced by bortezomib after SC administration. On the other hand, the QLQ-CIPN20 questionnaire (EORTC) evaluating the intensity of sensory, motor and autonomic disorders associated with CIPN has never been tested in this population. The objective of this study is twofold: (i) psychophysical evaluation of neuropathic disorders by studying the thermal and vibratory detection thresholds and thermal nociceptive thresholds and (ii) quantitative and qualitative assessment of neuropathic disorders by the QLQ-CIPN20 and related comorbidities in a population of neuropathic patients treated with bortezomib (n = 15), compared to control patients treated with bortezomib but non-neuropathic (n = 45).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Peripheral neuropathies induced by cancer chemotherapy (CIPN) remain a problem in oncology. These CIPN are induced by certain classes of chemotherapy such as taxanes (paclitaxel and docetaxel), platinum salts (cisplatin and oxaliplatin), alkaloids of the Madagascar periwinkle (vincristine), bortezomib, thalidomide and eribulin. These CIPN is essentially resulting in sensory disturbances such as paresthesia, dysesthesia or numbness. Unfortunately, no treatment can be offered as "gold standard" for preventing or treating the CIPN. Therefore, oncologists reduce or stop doses of chemotherapy because patients suffering from CIPN have a marked deterioration in their quality of life and suffer from comorbidities such as anxiety, depression and sleep disorders.

Among chemotherapy, bortezomib remains relatively understudied in terms of pathophysiology, compared to the platinum salts or taxanes, whereas the neurotoxicity of bortezomib remains a limiting factor for treatment. Currently, bortezomib is indicated for the treatment in 1st line of multiple myeloma in the following protocols:

  • Patients <65 years: Protocol VTD: Velcade (bortezomib), thalidomide, dexamethasone + autologous transplant
  • Patients> 65: Protocol MPV: Melphalan, Prednisone, Velcade. Or Protocol VD: Velcade, dexamethasone Since 2012, the FDA and the EMA have validated the subcutaneous administration of bortezomib instead of intravenously, in order to limit the adverse effects of bortezomib, including neurotoxicity. Indeed, a large study reported that the subcutaneous bortezomib allowed to keep the same therapeutic efficacy while improving the safety profile and in particular by limiting peripheral neuropathies (CIPN any grade: 38% vs 53%, grade ≥2: 24% vs 41%, grade ≥3 6% vs 16%). However, a recent retrospective study reported that the prevalence of peripheral neuropathies induced by bortezomib after subcutaneous administration remain relatively high: CIPN any grade: 41%, grade ≥2: 18% grade ≥3: 4 %, and especially that this prevalence of CIPN is no different between subcutaneous and intravenous route.

Bortezomib is administered subcutaneously to limit the appearance of neuropathic disorders and no study has evaluated quantitatively and qualitatively (QST) the sensory disorders in patients with peripheral neuropathies induced by bortezomib after subcutaneous administration. On the other hand, a measurement tool like the QLQ-CIPN20 questionnaire (EORTC) evaluating the intensity of sensory, motor and autonomic disorders associated with CIPN has never been tested in this patient population. While the questionnaire is presented as the most appropriate tool in the evaluation of CIPN.

Thus, the exploration of peripheral neuropathies induced by bortezomib after subcutaneous administration through QST (thermal) and QLQ-CIPN20 questionnaire would complement the clinical knowledge of the CIPN. This knowledge will be essential to propose and test new strategies for treatment and prevention of peripheral neuropathies induced by bortezomib.

The objective of this study is twofold: (i) psychophysical evaluation of neuropathic disorders by studying the QST (thermal and vibratory sensory thresholds, thermal nociceptive thresholds) and (ii) quantitative and qualitative assessment of neuropathic disorders by the QLQ -CIPN20 questionnaire (EORTC) and associated comorbidities in patients treated with bortezomib (subcutaneous administration).

Study Type

Observational

Enrollment (Anticipated)

60

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

  • France
      • Clermont-Ferrand, France, 63003
        • Recruiting
        • Chu Clermont-Ferrand
        • Principal Investigator:
          • Carine CHALETEIX

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

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

patients with myeloma multiple

Description

Inclusion Criteria:

  • Multiple myeloma diagnosis.
  • Patient undergoing or who received bortezomib-based chemotherapy in first-line (VTD protocol, MPV or VD).

Case Group: peripheral sensory neuropathy

  • Neuropathy ≥ grade 2 (grade 2-3) from NCI-CTCAE

Control group: asymptomatic

  • Neuropathy of grade <2 (grade 0-1) from NCI-CTCAE

Exclusion Criteria:

  • Age <18 years.
  • Treatment history by neurotoxic chemotherapy (taxanes, platinum salts, bortezomib, thalidomide, eribulin) before the current treatment.
  • Existing treatment: opioids, tricyclic antidepressants, pregabalin, gabapentin, duloxetine or AEDs.
  • Drinking: Male > 3 and Woman > 2 units per day.
  • Peripheral neuropathies history or known neuropathic pain
  • Progressive neurological disease.
  • Patient enrolled in a clinical study evaluating a preventive or curative treatment of chemotherapy-induced peripheral neuropathy.

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
patients with myeloma multiple
Other: bortezomib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Thermal sensory thresholds of sensitivity to hot measured using a thermode (Medoc TSA-II Abioz Technologies)
Time Frame: at day 1
at day 1
Sensory thresholds of patients will be measured using a thermode (Medoc TSA-II Abioz Technologies)
Time Frame: at day 1
at day 1
Thermal sensory thresholds will be reviewed at the thenar eminence of 2 hands
Time Frame: at day 1
at day 1

Secondary Outcome Measures

Outcome Measure
Time Frame
Sensitivity to heat, cold and vibration (will be measured using a thermode)
Time Frame: at day 1
at day 1
Pain induced by hot and cold (will be measured using a thermode)
Time Frame: at day 1
at day 1
Neuropathic symptoms (DN4 questionnaires)
Time Frame: at day 1
at day 1
Neuropathic symptoms (QLQ CIPN20 NPSI questionnaires)
Time Frame: at day 1
at day 1
Neuropathic pain (NRS) measured using a thermode (Medoc TSA-II Abioz Technologies)
Time Frame: at day 1
at day 1
Quality of life (QLQ-C30 questionnaires)
Time Frame: at day 1
at day 1
Quality of life (QLQ-MY20 questionnaires)
Time Frame: at day 1
at day 1
Depression (HADS questionnaire)
Time Frame: at day 1
at day 1

Collaborators and Investigators

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

Sponsor

University Hospital, Clermont-Ferrand

Collaborators

Laboratoires Takeda

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 (ACTUAL)

June 7, 2016

Primary Completion (ANTICIPATED)

December 31, 2020

Study Completion (ANTICIPATED)

January 31, 2021

Study Registration Dates

First Submitted

November 18, 2016

First Submitted That Met QC Criteria

November 28, 2016

First Posted (ESTIMATE)

November 29, 2016

Study Record Updates

Last Update Posted (ACTUAL)

July 1, 2019

Last Update Submitted That Met QC Criteria

June 28, 2019

Last Verified

November 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHU-0291
  • 2015-A01172-47 (OTHER: 2015-A01172-47)

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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