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

Not Applicable

Recruiting

• Conditions: Hand-Foot Skin Reaction (HFSR)
• Interventions: Dietary Supplement: Zinc Supplementation; Drug: Clobetasol Propionate 0.05% Cream

• Registration Number: NCT06856590
• Lead Sponsor: Gazi University

Brief Summary

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.

Detailed Description

Background and Rationale Hand-foot skin reaction (HFSR) is a common dose-limiting toxicity associated with regorafenib treatment, occurring in more than 50% of patients and leading to treatment modifications in up to 15% of cases. Despite its clinical significance, no standardized prophylactic strategy exists.

High-potency topical corticosteroids, such as clobetasol propionate 0.05%, have demonstrated efficacy in reducing HFSR severity, particularly when used preemptively. Additionally, recent studies suggest that oral zinc supplementation may contribute to maintaining skin integrity and reducing inflammatory responses, thereby mitigating HFSR severity. However, the comparative efficacy of these interventions and their potential synergistic effect have not been well established.

Study Objectives This study aims to evaluate whether oral zinc supplementation and/or transdermal clobetasol cream effectively prevent and reduce the severity of regorafenib-induced HFSR, thereby improving treatment adherence and patient quality of life.

Study Design

This is a prospective, non-randomized, interventional study involving approximately 120 patients receiving regorafenib at multiple oncology centers in Türkiye. Participants will be assigned to one of three intervention arms based on their treating physician's discretion:

Oral zinc supplementation + transdermal clobetasol cream Transdermal clobetasol cream alone Oral zinc supplementation alone Interventions Oral Zinc Supplementation: 78 mg zinc gluconate, administered twice daily for 8 weeks.

Transdermal Clobetasol Cream: Clobetasol propionate 0.05%, applied twice daily to the palms and soles for 8 weeks.

Assessment \& Follow-up HFSR severity and incidence will be evaluated using CTCAE v5.0 criteria. Patient-reported outcomes will be assessed via Hand-Foot Syndrome Scale-14 (HFS-14) and FACT-G quality of life questionnaire.

Regorafenib adherence (dose modifications, treatment discontinuations) will be monitored.

Survival analysis (PFS and OS) will be conducted at 6 months. By comparing these prophylactic strategies, this study seeks to identify the most effective approach to minimize HFSR burden in patients undergoing regorafenib therapy, potentially influencing future clinical practice.

Study Timeline

• Status Verified: 2025-02
• Study Start: 2025-02-20
• Study First Submitted: 2025-02-21
• Study First Submitted QC: 2025-02-26
• Study First Posted: 2025-03-04
• Last Update Submitted: 2025-06-01
• Last Update Posted: 2025-06-05
• Primary Completion: 2025-10-01
• Study Completion: 2026-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Zinc + Clobetasol Group	Zinc Supplementation	Participants in this group will receive oral zinc supplementation (78 mg zinc gluconate twice daily) combined with topical clobetasol propionate 0.05% cream, applied twice daily to the palms and soles for 8 weeks. This group aims to evaluate the combined efficacy of zinc and clobetasol in preventing regorafenib-induced hand-foot skin reaction (HFSR).
Zinc + Clobetasol Group	Clobetasol Propionate 0.05% Cream	Participants in this group will receive oral zinc supplementation (78 mg zinc gluconate twice daily) combined with topical clobetasol propionate 0.05% cream, applied twice daily to the palms and soles for 8 weeks. This group aims to evaluate the combined efficacy of zinc and clobetasol in preventing regorafenib-induced hand-foot skin reaction (HFSR).
Clobetasol Alone Group	Clobetasol Propionate 0.05% Cream	Participants in this group will receive topical clobetasol propionate 0.05% cream, applied twice daily to the palms and soles for 8 weeks. This group aims to assess the efficacy of clobetasol alone in preventing regorafenib-induced HFSR.
Zinc Alone	Zinc Supplementation	Participants in this group will receive oral zinc supplementation (78 mg zinc gluconate twice daily) for 8 weeks. This group aims to determine the role of zinc alone in reducing the severity of regorafenib-induced HFSR.

Primary Outcome Measures

Name	Time	Method
Incidence and Severity of Hand-Foot Skin Reaction (HFSR) at Week 8	8 weeks	The incidence and severity of hand-foot skin reaction (HFSR) will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The proportion of patients experiencing Grade ≥2 HFSR will be compared between the intervention groups to evaluate the efficacy of zinc supplementation and/or clobetasol in preventing HFSR.

Secondary Outcome Measures

Name	Time	Method
Duration of Hand-Foot Skin Reaction (HFSR)	8 weeks	The time from the onset of Grade ≥2 HFSR to its resolution (return to Grade 1 or lower) will be measured in each intervention group. The effectiveness of zinc supplementation and/or clobetasol in shortening HFSR duration will be evaluated.
Regorafenib Dose Modifications Due to HFSR	8 weeks	The percentage of participants requiring dose reduction, dose delay, or treatment discontinuation due to HFSR will be recorded. The impact of prophylactic zinc supplementation and/or clobetasol on maintaining regorafenib treatment adherence will be assessed.
Quality of Life (FACT-G Score Change)	Baseline and 8 weeks	Changes in quality of life (QoL) will be assessed using the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire. QoL scores at baseline and at Week 8 will be compared among the intervention groups. The FACT-G total score ranges from 0 to 108, with higher scores indicating better quality of life.
Progression-Free Survival (PFS) in Patients with and without Severe HFSR	Up to 6 months	The time from the start of regorafenib treatment to disease progression or death from any cause, whichever occurs first.
Overall Survival (OS) in Patients with and without Severe HFSR	6 months	The time from the start of regorafenib treatment to death from any cause.

Trial Locations

Locations (13)

Necmettin Erbakan University Meram Faculty of Medicine Hospital; 🇹🇷 Konya, Meram, Turkey

Bursa Uludağ University Hospital; 🇹🇷 Bursa, Nilüfer, Turkey

Karadeniz Technical University Hospital; 🇹🇷 Trabzon, Ortahisar, Turkey

Sakarya University Hospital; 🇹🇷 Sakarya, Serdivan, Turkey

Ankara Etlik City Hospital; 🇹🇷 Ankara, Yenimahalle, Turkey

Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital; 🇹🇷 Ankara, Yenimahalle, Turkey

Gazi University; 🇹🇷 Ankara, Yenimahalle, Turkey

Afyonkarahisar University of Health Sciences Hospital; 🇹🇷 Afyonkarahisar, Turkey

Ankara University Faculty of Medicine Hospital; 🇹🇷 Ankara, Turkey

Hacettepe University Faculty of Medicine Hospital; 🇹🇷 Ankara, Turkey

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