Compression Stockings to Prevent Peripheral Neuropathy Caused by Antibody-Drug Conjugates in Urothelial Carcinoma Patients

Sheng Zhang58 enrolled

Overview

This multicenter, prospective phase II clinical trial aims to evaluate the efficacy and safety of medical compression stockings in preventing peripheral neuropathy induced by antibody-drug conjugates (ADCs) containing monomethyl auristatin E (MMAE) in patients with advanced cancers, including urothelial carcinoma. Eligible participants will have no baseline ≥ grade 1 neuropathy and will be scheduled to receive MMAE-containing ADC therapy. A total of 58 patients will be enrolled and followed for 24 months. In this self-controlled design, the left foot will be fitted with a medical compression stocking while the right foot remains uncovered, starting 15 minutes before infusion and continuing until 15 minutes after infusion (total duration: 120 minutes). Peripheral neuropathy will be assessed before treatment, after cycle 3, within 1 week after treatment completion, and 1 month after completion, using CTCAE v5.0 and patient-reported questionnaires (QLQ-C30 and FACT-GOG-NTx). Toe temperature will be measured to assess local microcirculation changes. The study will also monitor compression-related adverse events. The results will provide evidence for preventive strategies to reduce ADC-induced peripheral neuropathy and improve patients' quality of life.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Urothelial Carcinoma Advanced Solid Tumors

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 18 years Histologically or cytologically confirmed advanced malignancy (including but not limited to urothelial carcinoma) eligible for MMAE-containing ADC therapy (e.g., EV, DV, BV) * ECOG performance status 0-2 * No baseline peripheral neuropathy ≥ Grade 1 (CTCAE v5.0) * Stable tumor status without other neurotoxic drugs in the past 2 months * Adequate organ function (blood counts, liver and kidney function) per protocol * Expected survival ≥ 3 months * Ability and willingness to comply with study procedures and provide written informed consent Exclusion Criteria: * Poor compliance or inability to follow protocol * Pre-existing peripheral neuropathy ≥ Grade 1 from prior platinum/taxane treatment * Severe diabetes or peripheral vascular disease * Neurological disorders causing nerve compression (e.g., carpal tunnel syndrome, radiculopathy) * Severe psychiatric conditions (depression, bipolar disorder, substance abuse) * Active uncontrolled infections requiring systemic antibiotics/antifungals/antivirals (≥ CTCAE Grade 2) * Active hepatitis or significant liver dysfunction not meeting inclusion criteria * Renal failure requiring dialysis * Immunodeficiency or history of organ transplantation * Severe nausea, headache, fatigue, or other debilitating symptoms * Active tuberculosis or uncontrolled pleural/pericardial effusion/ascites * Hypersensitivity to monoclonal antibodies or study device components * Participation in other clinical trials within 4 weeks * Known bleeding or coagulation disorders or receiving thrombolytic therapy * Any other condition judged by the investigator to preclude safe participation

Outcomes

Primary Outcomes

Incidence of Grade ≥1 Peripheral Neuropathy (CTCAE v5.0)

The proportion of patients who develop Grade ≥1 peripheral neuropathy, as assessed by CTCAE version 5.0.

Time frame: Baseline (within 7 days before treatment start); At the end of Cycle 3 (each cycle = 28 days, within 7 days); At treatment completion (within 7 days of last ADC dose); 1 month (±7 days) after treatment completion.

Secondary Outcomes

Change in Quality of Life Scores (EORTC QLQ-C30)

Change in patient-reported quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Scores range from 0 to 100; higher scores indicate better quality of life.

Time frame: Baseline; At the end of Cycle 3 (each cycle = 28 days); At treatment completion (within 7 days of last ADC dose); 1 month (±7 days) after treatment completion.

Peripheral Neuropathy Severity (FACT-GOG-NTx Scale)

Severity of chemotherapy-induced neuropathy symptoms assessed by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-NTx) subscale. Scores range from 0 to 44; higher scores indicate more severe neuropathy.

Time frame: Baseline; At the end of Cycle 3 (each cycle = 28 days); At treatment completion (within 7 days of last ADC dose); 1 month (±7 days) after treatment completion.

Left vs. Right Lower Limb Neuropathy Comparison (FACT-GOG-NTx Scale)

Assessment of lower limb neuropathy symptoms, focusing on sensory and motor impairment, using a 4-item subscale from the FACT-GOG-NTx questionnaire. Each item is scored from 0 to 4, with total scores ranging from 0 to 16; higher scores indicate more severe neuropathy.

Time frame: Baseline; At the end of Cycle 3 (each cycle = 28 days); At treatment completion (within 7 days of last ADC dose); 1 month (±7 days) after treatment completion

Incidence of Grade ≥2 Peripheral Neuropathy (CTCAE v5.0)

Proportion of patients developing Grade 2 or higher peripheral neuropathy as per CTCAE 5.0 criteria.

Time frame: Measured at baseline, after the 3rd treatment cycle, at treatment completion, and 1 month after treatment completion.

Toe Temperature Changes (Infrared Thermography)

Change in toe temperature measured using infrared thermography, as an indicator of local microcirculation changes.

Time frame: Baseline (within 7 days before treatment start); At the end of Cycle 3 (each cycle = 28 days, within 7 days).