A Multicenter, Prospective, Phase II Clinical Trial Investigating the Use of Compression Stockings to Prevent Peripheral Neuropathy Induced by Antibody-Drug Conjugates (ADCs) in Patients With Urothelial Carcinoma
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 58
- Locations
- 1
- Primary Endpoint
- Incidence of Grade ≥1 Peripheral Neuropathy (CTCAE v5.0)
Study Overview
Brief Summary
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 Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Compression Stocking Arm
Each participant will wear a medical-grade compression stocking (Class II, 20-30 mmHg) on the assigned foot throughout the entire treatment period with antibody-drug conjugates (ADCs). Stockings are worn daily except during bathing.
Intervention: Medical-grade compression stocking (Device)
Control Arm (No Stocking)
The contralateral foot will not receive any compression stocking and will be observed under the same ADC treatment conditions. Each participant serves as their own control.
Outcomes
Primary Outcomes
Incidence of Grade ≥1 Peripheral Neuropathy (CTCAE v5.0)
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.
The proportion of patients who develop Grade ≥1 peripheral neuropathy, as assessed by CTCAE version 5.0.
Secondary Outcomes
- Change in Quality of Life Scores (EORTC QLQ-C30)(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)(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)(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)(Measured at baseline, after the 3rd treatment cycle, at treatment completion, and 1 month after treatment completion.)
- Toe Temperature Changes (Infrared Thermography)(Baseline (within 7 days before treatment start); At the end of Cycle 3 (each cycle = 28 days, within 7 days).)
Investigators
Sheng Zhang
Prof.
Fudan University