ZINCLO-HAND: Zinc and Clobetasol for the Prevention of Regorafenib-Induced Hand-Foot Skin Reaction

This study aims to evaluate whether a combination of oral zinc supplementation and transdermal clobetasol cream is effective in preventing and reducing the severity of hand-foot skin reaction (HFSR) induced by regorafenib treatment. HFSR is one of the most common adverse effects of regorafenib, affecting more than 50% of patients, with 10-15% experiencing severe Grade 3 toxicity. Clobetasol, a high-potency corticosteroid, has been shown to significantly reduce the severity of HFSR when used preemptively rather than reactively. Additionally, recent clinical trials indicate that oral zinc supplementation may further reduce the incidence of Grade ≥2 HFSR. This prospective, non-randomized interventional study will compare three treatment groups: Oral zinc supplementation + transdermal clobetasol cream Transdermal clobetasol cream alone Oral zinc supplementation alone The study will assess the effectiveness of these treatments using CTCAE grading, the Hand-Foot Syndrome Scale-14, and quality of life measures (FACT-G, fatigue, and anxiety/depression scales). Additionally, the study will evaluate the impact of HFSR on treatment adherence, regorafenib dose modifications, and overall survival. The study will enroll approximately 120 patients across multiple centers in Türkiye.

Sex

All

Minimum age

18 Years

Maximum age

80 Years

Inclusion Criteria:

* Age ≥18 years
* Histologically confirmed solid tumor for which regorafenib is an approved treatment (e.g., metastatic colorectal cancer, gastrointestinal stromal tumor, hepatocellular carcinoma, glioblastoma, or others)
* Initiating regorafenib treatment for the first time
* ECOG performance status of 0-2
* Baseline hand-foot skin reaction (HFSR) of Grade 0 (no prior HFSR symptoms) according to CTCAE v5.0
* Adequate organ function, including:

AST/ALT ≤ 3× upper limit of normal (ULN) Creatinine clearance \> 50 mL/min Hemoglobin ≥ 9 g/dL Platelet count ≥ 75,000/mm³

* Able to tolerate oral zinc supplementation and/or topical corticosteroids
* Willing to participate and provide informed consent

Exclusion Criteria:

* Pre-existing dermatologic conditions affecting the hands or feet (e.g., psoriasis, eczema, active infections)
* Prior Grade ≥1 HFSR from any VEGFR-TKI therapy
* Allergy or known hypersensitivity to zinc, clobetasol, or other study components