International CIPN Assessment and Validation Study

Quality of Life Clinical Trial

— ICAVS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04633655
• Other study ID #: ICAVS
• Status: Recruiting
• Start date: June 8, 2020
• Est. completion date: October 1, 2025

Study information

• Verified date: May 2023
• Source: University of Milano Bicocca
• Contact: GUIDO CAVALETTI, MD
• Phone: + 39 02 6448 8039
• Email: guido.cavaletti[@]unimib.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: October 1, 2025
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chemotherapy-induced Peripheral Neuropathy
• Peripheral Nervous System Diseases
• Quality of Life

Intervention

Other:
• outcome measures for CIPN testing
questionnaires administration, physician based scales for CIPN data collection

Locations

Country	Name	City	State
Australia	Brain and Mind Center	Sidney
Austria	Dept. of Neurology, Medical University of Vienna	Vienna
Bangladesh	International Centre for Diarrhoeal Disease Research	Dhaka
Brazil	Clínica AMO	Salvador
Canada	The Ottawa Hospital	Ottawa
Denmark	Aarhus University Hospital	Aarhus
France	Hôpital Percy	Clamart
France	CHU Dupuytren	Limoges
Germany	Center for Molecular Medicine	Cologne
Greece	University of Larissa	Larissa
Greece	"Saint Andrew's" State General Hospital	Patras
Italy	Ospedale Valduce	Como
Italy	Ospedale Policlinico San Martino	Genova
Italy	A.O.U. Policlinico "G. Martino"	Messina
Italy	San Gerardo Hospital	Monza	Mb
Italy	Padova Hospital	Padova
Italy	Azienda Ospedaliera Universitaria	Verona
Kenya	Medical Oncoloy Unit - University of Nairobi	Nairobi
Korea, Republic of	Dong-A University - Internal Medicine Dept.	Busan
Portugal	Centro Hospitalar Vila Nova de Gaia/Espinho	Vila Nova de Gaia
Spain	Hospital Universitari de Bellvitge-ICO L'Hospitalet	Barcelona
Switzerland	University of Basel - Department of Sport, Exercise and Health	Basel
United States	University of Michigan School of Nursing	Ann Arbor	Michigan
United States	Northside Hospital	Atlanta	Georgia
United States	JHU	Baltimore	Maryland
United States	Birmingham School of Nursing, University of Alabama	Birmingham	Alabama
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Cancer Center/Wexner Medical Center - Ohio State Medical Oncology Division	Columbus	Ohio
United States	Dartmouth-Hitchcock Medical Center	Lebanon	Pennsylvania
United States	Columbia University Irving Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
University of Milano Bicocca

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Bangladesh,  Brazil,  Canada,  Denmark,  France,  Germany,  Greece,  Italy,  Kenya,  Korea, Republic of,  Portugal,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Chemotherapy-induced peripheral neurotoxicity as assessed by change in NCI-CTC v.5 sensory and motor grade	NCI-CTC v.5 sensory and motor (changes from base line to end treatment of a 0-5 score)	5 YEARS
Primary	Chemotherapy-induced peripheral neurotoxicity as assessed by change in PRO-CTCAE	PRO-CTCAE (changes from base line to end treatment of a 0-5 score for each item)	5 YEARS
Primary	Chemotherapy-induced peripheral neurotoxicity as assessed by change in Pain Intensity Numerical Rating Scale (PI-NRS)	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
Primary	Chemotherapy-induced peripheral neurotoxicity as assessed by change in NPS-CIN scale	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
Primary	Chemotherapy-induced peripheral neurotoxicity as assessed by change in EORTC CIPN20© scale	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
Primary	Chemotherapy-induced peripheral neurotoxicity as assessed by change in FACT-GOG NTX v.4© scale	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
Primary	Chemotherapy-induced peripheral neurotoxicity as assessed by change in TNSn© scale	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
Primary	Chemotherapy-induced peripheral neurotoxicity as assessed by change in PGIC scale	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
Primary	Chemotherapy-induced peripheral neurotoxicity as assessed by change in OXA-NQ scale	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	Chemotherapy-induced peripheral neurotoxicity as assessed by change in EORTC CIPN15 scale	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
Secondary	Chemotherapy-induced peripheral neurotoxicity as assessed by change in TNSc© scale	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
Secondary	Chemotherapy-induced peripheral neurotoxicity as assessed by change in nerve conduction studies	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
Secondary	Chemotherapy-induced peripheral neurotoxicity as assessed by change in Quantitative sensory testing (QST)	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
Secondary	Chemotherapy-induced peripheral neurotoxicity as assessed by change in neurofilament light chain (NfL) levels	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
Secondary	Chemotherapy-induced peripheral neurotoxicity as assessed by change in DN4 scale	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