Advanced Solid Tumors, Antibody-drug Conjugates, Chemotherapy-Induced Peripheral Neuropathy, Urothelial Carcinoma
Conditions
Keywords
Antibody-Drug Conjugates, Peripheral Neuropathy Prevention, Compression Stockings, Advanced Cancer, Quality of Life, Mechanical Compression Therapy
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.
Interventions
DEVICEMedical-grade compression stocking
A knee-high compression stocking providing 20-30 mmHg pressure will be applied to the assigned foot during the ADC treatment period to prevent chemotherapy-induced peripheral neuropathy (CIPN). Stockings will be worn daily, except during bathing.
Sponsors
Sheng Zhang
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Self-controlled, within-subject comparison: left foot receives compression stocking, right foot serves as control.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Grade ≥1 Peripheral Neuropathy (CTCAE v5.0) | 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
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. |
| 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. | 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. |
| 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 | 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. |
| 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. | Proportion of patients developing Grade 2 or higher peripheral neuropathy as per CTCAE 5.0 criteria. |
| 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). | Change in toe temperature measured using infrared thermography, as an indicator of local microcirculation changes. |
Countries
China
Contacts
Primary ContactSheng Zhang, PhD
Outcome results
None listed