The CONTRoL Trial: Cryotherapy vs. cOmpression Neuropathy TRiaL

Not Applicable

Completed

• Conditions: CIPN - Chemotherapy-Induced Peripheral Neuropathy
• Interventions: Device: Cryotherapy; Device: Compression Therapy; Device: Loose glove/sock

• Registration Number: NCT03873272
• Lead Sponsor: Columbia University

Brief Summary

The primary objective of this study is to select the best intervention from cold therapy, compression therapy and placebo at reducing neuropathic pain as measured by the change in the Neurotoxicity (NTX) component of the Functional Assessment of Cancer Therapy (FACT) - Taxane questionnaire, following 12 weeks of neoadjuvant/adjuvant chemotherapy with paclitaxel or docetaxel among breast cancer patients.

Detailed Description

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent side effect resulting from the administration of cytotoxic chemotherapeutic agents. The incidence of CIPN can vary on the type of agent used, the frequency with which it is given, and the cumulative dose. Unfortunately, for some patients, symptoms may persist even after discontinuation of the drug due to irreversible nerve damage. As of now, there are no established agents for CIPN prevention.

This is a randomized, placebo-controlled clinical selection trial of interventions for CIPN in patients treated with docetaxel every 3 weeks or paclitaxel on a weekly schedule. Patients will be randomly assigned to receive either frozen gloves and socks, compression gloves and socks, or "loose" gloves and socks (placebo arm) during chemotherapy infusion to study the best intervention at reducing neuropathic pain.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2019-03-12
• Study First Submitted QC: 2019-03-12
• Study First Posted: 2019-03-13
• Study Start: 2019-04-25
• Primary Completion: 2022-09-12
• Study Completion: 2023-02-02
• Results First Submitted: 2023-04-28
• Results First Submitted QC: 2023-04-28
• Results First Posted: 2023-05-25
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-10
• Last Update Posted: 2024-10-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 63

Inclusion Criteria

• Age greater or equal to 18 years.
• History of stage I-III breast cancer
• Patient scheduled to be receiving adjuvant or neoadjuvant paclitaxel or docetaxel for at least 12 weeks
• Signed informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%,)

Read More

Exclusion Criteria

• Prior treatment with taxane or platinum based chemotherapy
• Known history of neuropathy
• Raynaud's phenomenon
• Peripheral arterial ischemia
• Cold intolerance
• Current use of duloxetine which may mitigate chemotherapy-induced peripheral neuropathy (CIPN)

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cryotherapy	Cryotherapy	Men or women over the age of 18 with a history of stage I-III breast cancer and is scheduled to receive adjuvant or neoadjuvant paclitaxel or docetaxel for at least 12 weeks.
Compression Therapy	Compression Therapy	Men or women over the age of 18 with a history of stage I-III breast cancer and is scheduled to receive adjuvant or neoadjuvant paclitaxel or docetaxel for at least 12 weeks.
Control arm (Loose glove/sock)	Loose glove/sock	Men or women over the age of 18 with a history of stage I-III breast cancer and is scheduled to receive adjuvant or neoadjuvant paclitaxel or docetaxel for at least 12 weeks.

Primary Outcome Measures

Name	Time	Method
Proportion of Patients With Successful Outcomes (<5-point Decrease in FACT-NTX From Baseline)	Baseline, 12 weeks	The primary endpoint is the change in FACT NTX at 12 weeks from the start of chemotherapy. The change in FACT NTX will be dichotomized into a good outcome (change in FACT NTX less than 5 from baseline to week 12) versus a poor outcome (change in FACT NTX greater than or equal to 5 from baseline to week 12). The FACT-NTX subscale includes 11 items, each of which is divided into 5 scoring levels: 0, 1, 2, 3, 4, and a total score of 44. The scale is graded 0-4. A low score indicates a good effect. This change in FACT-NTX scale score indicates the proportion of patients with successful outcomes.

Secondary Outcome Measures

Name	Time	Method
Change in NCI-CTCAE Grade for CIPN	Baseline, 12, and 24 weeks	National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) is a subjective method to evaluate CIPN which is performed by a healthcare professional. The patient's peripheral sensory neuropathy, peripheral motor neuropathy, dysesthesia, paresthesia and neuralgia will be graded on a scale of 1 to 5 depending on severity with 1 indicating a better outcome.
Change in Nail Toxicity	Baseline, 12 weeks, 24 weeks	The number of participants with a change in cutaneous toxicity and onycholysis will be assessed by a healthcare professional using the National Cancer Institute Common Toxicity Criteria (Version 2), specifically nail changes. Grade 1 includes discoloration, ridging (koilonychia), or pitting of the nails and Grade 2 is partial or complete loss of nail(s) or pain in the nail beds. A higher grade indicates more nail toxicity.
Comfort With Intervention Scale Score	Up to 24 weeks	Comfort with the study intervention will be assessed on a 4-point scale, (0=dissatisfied; 1=not satisfied; 2=satisfied; 3=very satisfied) with 3 indicating a better outcome.
Vibration Perception and Disappearance Threshold	Up to 24 weeks	Study participants will be assessed for development of sensory neurological dysfunction. Vibration perception will be assessed using a tuning fork. Vibration threshold will be tested on the bilateral dorsum of the distal interphalangeal joint of the index finger and dorsum of the interphalangeal joint of the hallux. Subjects will be asked to indicate when the vibration stimulus is initially felt (perception threshold) and when the stimulus disappears (disappearance threshold.) The vibration perception threshold is the average of three paired measurements.
Subjects Perceived Pain and Pressure Using Neuropen Test	Up to 24 weeks	Evaluation of other sensory endpoints including touch, pressure and pain will be evaluated using a Neuropen. Touch and pressure sensation will be assessed using a 10-g monofilament on the subject's dominant foot. Pain and subjective sharpness sensation will be assessed using the Neuropen on the dominant foot. The spring mechanism is calibrated to exert a force of 40 grams to help identify subjects with loss of pain sensation. Ten points on the foot are tested. If the participant detects pain and pressure on less than 8 points, pain and pressure perception are considered diminished. Perception on 8 points of the foot or greater is considered a better outcome.
Average Time to Complete 'Timed Get up and go' Test	Up to 24 weeks	The 'timed get up and go' test is a rapid and widely used clinical performance-based measure of lower extremity function, mobility, and fall risk. Subjects are asked to stand up from a standard chair (seat height between 44 and 47 cm), walk a distance of 3 m (marked on the floor) at a comfortable pace, turn, walk back and sit down. Time will be measured in seconds. Shorter times indicate better performance.
Tandem and Unipedal Stance Test	Up to 24 weeks	Balance will be assessed using the tandem and unipedal stance test. In this assessment, the subject stands with one foot in front of the other (heel to toe) (30 seconds), then on one leg with: eyes open (60 seconds), eyes closed (30 seconds), and eyes open with head rotation (30 seconds) with arms held comfortably at the side. The test was accepted failure when the stance foot shifted in any way or the nonstance foot touched the ground. Tests are recorded as achieved (yes) or not achieved (no).
Adherence to Study Intervention	Up to 24 weeks	The number of participants who adhered to the intervention. Adherence is defined as wearing the assigned gloves and socks for greater than or equal to 80% of infusions.

Trial Locations

Locations (1)

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States