International CIPN Assessment and Validation Study (ICAVS)

May 24, 2023 updated by: University of Milano Bicocca

International Chemotherapy Induced Peripheral Neurotoxicity (CIPN) Assessment and Validation Study

This is an observational study of chemotherapy-induced peripheral neurotoxicity (CIPN) patients to be investigated prospectively in order to assess responsiveness of a set of outcome measures in an international multi-center study.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study will be performed at all participating centers and will consist of the following assessments:

Core study (assessments at baseline and at the end of treatment)

  • Standard oncology assessment per local site
  • NCI-CTC (national cancer institute common toxicity criteria) v.5 sensory and motor
  • PRO-CTCAE (patient reported outcome-cancer common tocixity adverse event)
  • PI-NRS (pain intensity numeric rating scale)
  • NPS-CIN (Neuropathic Pain Scale for chemotherapy-induced neuropathy)
  • EORTC CIPN20© (The European Organisation of Research and Treatment of. Cancer Quality of Life Questionnaire-CIPN twenty-item scale)
  • FACT-GOG NTX v.4© (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity)
  • TNSn© (total neuropathy score, nurse version)
  • PGIC (patient global impression of change)
  • OXA-NQ (oxaliplatin neurotoxicity questionnaire)

Extended study (at all available sites - any combination of assessment methods is allowed, minimum at baseline and at the end of treatment)

  • EORTC CIPN15
  • CIPN-R-ODS (CIPN Rash overall disability scale)
  • TNSc© at the same time points as for questionnaire
  • OXA-NQ (also at mid-treatment)
  • nerve conduction study of the radial (motor and sensory), ulnar (motor and sensory), sural, dorsal sural and common peroneal nerves (*)
  • QST (*) [quantitative sensory testing]
  • Serum for biomarkers search (*)
  • DN4

Rationale: Within a multi-center international collaboration among experienced neurologists, oncologists, nurses and symptom scientists, the principal aim of this study is to evaluate responsiveness of a set of outcome measures for CIPN evaluation in order to define the gold standard for its assessment.

The assessment of CIPN will be performed at different levels of investigation. The Core study will allow the evaluation of subjects with common devices, so that an assessment can be performed at any medical site (expected time for questionnaires completion 15 minutes).

The Extended study will add any combination of the listed assessment methods/biological sample collection, in order to ascertain whether this approach can provide a more careful and clinically-relevant estimate of the peripheral nervous system damage. Comparison between healthcare evaluation and subjects' report of CIPN severity using established questionnaires will be performed in both Core and Extended studies.

Aims: The primary aim for this study is to test responsiveness of the different assessment methods used in the core study, in a multi-center, multi-regional International setting, comparing changes from baseline to end of treatment. Secondary aims are:

  • to evaluate responsiveness (changes from base line to end of treatment) also of the other outcome measures used in the Extended Study;
  • to evaluate mid-treatment data predictiveness of end of treatment neurological status for each outcome measure;
  • to evaluate recovery rate/modification of the neurological status for the follow up evaluations (3/6/12/24 months after treatment), stratifying data for different drugs.

Study Design: 1000 patients who are candidates for neurotoxic chemotherapy for any cancer with non-investigational drugs (including immune checkpoint inhibitors and "targeted" drugs) will be enrolled from participating centers. A trained investigator in each participating center will perform the selected healthcare-assessed scales and supervise the patient-completed measures as presented in Table 1. Subjects will be examined at least at baseline and end of treatment (Core Study) and at additional intermediate and follow-up timepoints (Extended study), according to their treatment plan.

Study Treatments: There are no study-specified treatments, as subjects will receive only their standard of care chemotherapy. The investigators will not influence decisions regarding treatment duration nor supply medication for this study. However, all treatment regimens will be registered.

Participating Centers minimum requirements: Participating Centers should:

  1. accept the study protocol and have their participation approved by a local Ethics Committee/Institutional Review Board
  2. have access through an internet connection to the secure server located at the main site
  3. guarantee the proper assessment of the selected patients at least at the Core study level
  4. have the potential to recruit at least 30 patients/year
  5. have the capacity to upload the data collected from each patient within 1 week

Study Type

Observational

Enrollment (Estimated)

1000

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • Australia
      • Sidney, Australia
        • Not yet recruiting
        • Brain and Mind Center
        • Contact:
  • Austria
      • Vienna, Austria
        • Not yet recruiting
        • Dept. of Neurology, Medical University of Vienna
        • Contact:
  • Bangladesh
      • Dhaka, Bangladesh
        • Not yet recruiting
        • International Centre for Diarrhoeal Disease Research
        • Contact:
  • Brazil
      • Salvador, Brazil
        • Not yet recruiting
        • Clinica AMO
        • Contact:
  • Canada
      • Ottawa, Canada
        • Not yet recruiting
        • The Ottawa Hospital
        • Contact:
          • Kristopher Dennis, MD
          • Phone Number: 70212 613) 737-7700
          • Email: krdennis@toh.ca
  • Denmark
      • Aarhus, Denmark
        • Withdrawn
        • Aarhus University Hospital
  • France
      • Clamart, France
        • Not yet recruiting
        • Hôpital Percy
        • Contact:
      • Limoges, France
        • Not yet recruiting
        • Chu Dupuytren
        • Contact:
  • Germany
      • Cologne, Germany
        • Not yet recruiting
        • Center for Molecular Medicine
        • Contact:
  • Greece
      • Larissa, Greece
        • Not yet recruiting
        • University of Larissa
        • Contact:
          • Efthmios Efthmios Dardiotis, MD
          • Phone Number: +302410685651
          • Email: edar@med.uth.gr
      • Patras, Greece
        • Recruiting
        • "Saint Andrew's" State General Hospital
        • Contact:
  • Italy
      • Como, Italy, 22063
        • Withdrawn
        • Ospedale Valduce
      • Genova, Italy
      • Messina, Italy
      • Padova, Italy
        • Not yet recruiting
        • Padova Hospital
        • Contact:
      • Verona, Italy
        • Not yet recruiting
        • Azienda Ospedaliera Universitaria
        • Contact:
    • Mb
  • Kenya
      • Nairobi, Kenya
        • Not yet recruiting
        • Medical Oncoloy Unit - University of Nairobi
        • Contact:
  • Korea, Republic of
      • Busan, Korea, Republic of
        • Recruiting
        • Dong-A University - Internal Medicine Dept.
        • Contact:
  • Portugal
      • Vila Nova de Gaia, Portugal
        • Not yet recruiting
        • Centro Hospitalar Vila Nova de Gaia/Espinho
        • Contact:
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Hospital Universitari de Bellvitge-ICO L'Hospitalet
        • Contact:
  • Switzerland
      • Basel, Switzerland
        • Not yet recruiting
        • University of Basel - Department of Sport, Exercise and Health
        • Contact:
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Not yet recruiting
        • Birmingham School of Nursing, University of Alabama
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30342
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Not yet recruiting
        • JHU
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Not yet recruiting
        • University of Michigan School of Nursing
        • Contact:
    • New York
      • New York, New York, United States, 10027
        • Not yet recruiting
        • Columbia University Irving Medical Center
        • Contact:
    • Ohio
      • Columbus, Ohio, United States, 43220
        • Not yet recruiting
        • Cancer Center/Wexner Medical Center - Ohio State Medical Oncology Division
        • Contact:
    • Pennsylvania
      • Lebanon, Pennsylvania, United States, 03756
    • Vermont
      • Burlington, Vermont, United States, 05445
        • Not yet recruiting
        • University of Vermont Medical Center
        • Contact:

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

Sampling Method

Non-Probability Sample

Study Population

Consecutive patients candidated to neurotoxic chemotherapy

Description

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for enrolment into the study:

  1. Subjects must be candidates for neurotoxic chemotherapy at doses expected to be potentially neurotoxic (a list of neurotoxic drugs is provided in Appendix 1).
  2. Male and female subjects who are 18 years of age or older.
  3. Subjects freely provide informed consent by signing and dating an informed consent form prior to study entry.
  4. Subjects must be willing to complete all study-related activities and follow-up visits required by the protocol.
  5. Subjects must have a Karnofsky performance score greater than or equal to 70. Exclusion Criteria

Subjects presenting with any of the following will not be included in the study:

  1. Poor prognosis, with high probability to be unable to complete the planned chemotherapy treatment.
  2. Concomitant neurologic conditions (e.g., brain tumor, spinal or brain metastases) that would interfere or complicate the assessments.
  3. Severe depression that in the opinion of the Investigator would complicate the assessments.
  4. Chronic treatment with antiepileptic drugs, antidepressants and major analgesics, unless stable dosing and conditions have been reached for 3 months prior to entry.
  5. Preventive interventions (e.g., antioxidants, cryotherapy, distal pressure).
  6. Subjects who are currently receiving another medication other than antineoplastic chemotherapy drugs that has known potential to produce neurologic peripheral nerve toxicity (e.g. metronidazole, isoniazid, amiodarone, antiretroviral medications).
  7. Subjects with any other condition, which, in the investigator's judgment, might decrease the chance of obtaining satisfactory data to achieve the objectives of the study.
  8. Previous neurotoxic chemotherapy.

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients who are receiving a neurotoxic chemotherapy

List of neurotoxic drugs eligible for enrolment

  • Platinum drugs
  • Taxanes
  • Vinca alkaloids
  • Epothilones
  • Proteasome inhibitors
  • Thalidomide
  • Vedotin-based drugs
  • checkpoint inhibitors
  • Any combination of the aforementioned drugs
Other: outcome measures for CIPN testing
questionnaires administration, physician based scales for CIPN data collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Chemotherapy-induced peripheral neurotoxicity as assessed by change in NCI-CTC v.5 sensory and motor grade
Time Frame: 5 YEARS
NCI-CTC v.5 sensory and motor (changes from base line to end treatment of a 0-5 score)
5 YEARS
Chemotherapy-induced peripheral neurotoxicity as assessed by change in PRO-CTCAE
Time Frame: 5 YEARS
PRO-CTCAE (changes from base line to end treatment of a 0-5 score for each item)
5 YEARS
Chemotherapy-induced peripheral neurotoxicity as assessed by change in Pain Intensity Numerical Rating Scale (PI-NRS)
Time Frame: 5 YEARS
difference between baseline and end of treatment of chemotherapy-induced peripheral neurotoxicity as assessed by change in Pain Intensity Numerical Rating Scale (PI-NRS) (0-10 score).
5 YEARS
Chemotherapy-induced peripheral neurotoxicity as assessed by change in NPS-CIN scale
Time Frame: 5 YEARS
difference between baseline and end of treatment of chemotherapy-induced peripheral neurotoxicity as assessed by change in NPS-CIN (changes from base line to end treatment of a 0-10 score)
5 YEARS
Chemotherapy-induced peripheral neurotoxicity as assessed by change in EORTC CIPN20© scale
Time Frame: 5 YEARS
difference between baseline and end of treatment of chemotherapy-induced peripheral neurotoxicity as assessed by change in EORTC CIPN20© (changes from base line to end treatment of a 0-100 score)
5 YEARS
Chemotherapy-induced peripheral neurotoxicity as assessed by change in FACT-GOG NTX v.4© scale
Time Frame: 5 YEARS
difference between baseline and end of treatment of chemotherapy-induced peripheral neurotoxicity as assessed by change in FACT-GOG NTX v.4© (changes from base line to end treatment of a 0-44 score)
5 YEARS
Chemotherapy-induced peripheral neurotoxicity as assessed by change in TNSn© scale
Time Frame: 5 YEARS
difference between baseline and end of treatment of chemotherapy-induced peripheral neurotoxicity as assessed by change in TNSn© (changes from base line to end treatment of a 0-20 score)
5 YEARS
Chemotherapy-induced peripheral neurotoxicity as assessed by change in PGIC scale
Time Frame: 5 YEARS
difference between baseline and end of treatment of chemotherapy-induced peripheral neurotoxicity as assessed by change in PGIC (changes from base line to end treatment of a 0-10 score)
5 YEARS
Chemotherapy-induced peripheral neurotoxicity as assessed by change in OXA-NQ scale
Time Frame: 5 YEARS
difference between baseline and end of treatment of chemotherapy-induced peripheral neurotoxicity as assessed by change in OXA-NQ (changes from base line to end treatment of number of symptoms: this is a yes/no questionnaire for the presence of neuropathy symptoms)
5 YEARS

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Chemotherapy-induced peripheral neurotoxicity as assessed by change in EORTC CIPN15 scale
Time Frame: 7 YEARS
difference between baseline and end of treatment of chemotherapy-induced peripheral neurotoxicity as assessed by change in EORTC CIPN15 (changes of the global score of this questionnaire, 0-60)
7 YEARS
Chemotherapy-induced peripheral neurotoxicity as assessed by change in TNSc© scale
Time Frame: 7 YEARS
difference between baseline and end of treatment of chemotherapy-induced peripheral neurotoxicity as assessed by change in TNSc© (changes of the global score of this physician base scale ranging 0-48)
7 YEARS
Chemotherapy-induced peripheral neurotoxicity as assessed by change in nerve conduction studies
Time Frame: 7 YEARS
difference between baseline and end of treatment of chemotherapy-induced peripheral neurotoxicity as assessed by change in nerve conduction study of the radial (motor and sensory), ulnar (motor and sensory), sural, dorsal sural and common peroneal nerves. Amplitude (microV for sensory and mV for motor recordings) and velocity (m/sec) will be obtained. A decrease under the normative values at all time points respect to base line will be considered as sign of neuropathy.
7 YEARS
Chemotherapy-induced peripheral neurotoxicity as assessed by change in Quantitative sensory testing (QST)
Time Frame: 7 YEARS
difference between baseline and end of treatment of chemotherapy-induced peripheral neurotoxicity as assessed by change in QST: scores in seconds for time to pain onset and pain intensity (0=no pain; 10=worst pain
7 YEARS
Chemotherapy-induced peripheral neurotoxicity as assessed by change in neurofilament light chain (NfL) levels
Time Frame: 7 YEARS
difference between baseline and end of treatment of chemotherapy-induced peripheral neurotoxicity as assessed by change in Serum for biomarkers search: NfL dosage (pg/mL)
7 YEARS
Chemotherapy-induced peripheral neurotoxicity as assessed by change in DN4 scale
Time Frame: 7 YEARS
difference between baseline and end of treatment of chemotherapy-induced peripheral neurotoxicity as assessed by change in DN4 (this is a scale ranging 0-10)
7 YEARS

Collaborators and Investigators

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

Sponsor

University of Milano Bicocca

Investigators

  • Study Chair: GUIDO CAVALETTI, MD, University of Milano Bicocca
  • Principal Investigator: PAOLA ALBERTI, MD, University of Milano Bicocca

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 8, 2020

Primary Completion (Estimated)

May 1, 2024

Study Completion (Estimated)

October 1, 2025

Study Registration Dates

First Submitted

June 9, 2020

First Submitted That Met QC Criteria

November 12, 2020

First Posted (Actual)

November 18, 2020

Study Record Updates

Last Update Posted (Actual)

May 25, 2023

Last Update Submitted That Met QC Criteria

May 24, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ICAVS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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