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

NCT06856590 | Completed

• 2 other identifiers: AESH-EK-2025-042Ankara Etlik City Hospital EC
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 13

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.

Conditions

Hand-Foot Skin Reaction (HFSR)

Keywords

Regorafenib-Induced Skin Toxicity; Clobetasol; Zinc Supplementation; Metastatic Colorectal Cancer (mCRC); Gastrointestinal Stromal Tumor (GIST); Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (1)

• Incidence and Severity of Hand-Foot Skin Reaction (HFSR) at Week 8

  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.

  8 weeks

Secondary Outcomes (5)

• Duration of Hand-Foot Skin Reaction (HFSR)

  8 weeks

• Regorafenib Dose Modifications Due to HFSR

  8 weeks

• Quality of Life (FACT-G Score Change)

  Baseline and 8 weeks

• Progression-Free Survival (PFS) in Patients with and without Severe HFSR

  Up to 6 months

• Overall Survival (OS) in Patients with and without Severe HFSR

  6 months

Study Arms (3)

Zinc + Clobetasol Group

EXPERIMENTAL

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).

Dietary Supplement: Zinc Supplementation; Drug: Clobetasol Propionate 0.05% Cream

Clobetasol Alone Group

EXPERIMENTAL

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.

Drug: Clobetasol Propionate 0.05% Cream

Zinc Alone

EXPERIMENTAL

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.

Dietary Supplement: Zinc Supplementation

Interventions

Zinc Supplementation DIETARY_SUPPLEMENT

Participants assigned to zinc-containing arms will receive oral zinc gluconate supplementation (78 mg twice daily) for 8 weeks. This intervention aims to evaluate the effect of zinc in preventing and reducing the severity of regorafenib-induced hand-foot skin reaction (HFSR).

Zinc + Clobetasol Group; Zinc Alone

Clobetasol Propionate 0.05% Cream DRUG

Participants assigned to clobetasol-containing arms will receive topical clobetasol propionate 0.05% cream, applied twice daily to the palms and soles for 8 weeks. This intervention aims to assess the efficacy of clobetasol in preventing regorafenib-induced HFSR.

Clobetasol Alone Group; Zinc + Clobetasol Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gazi University: lead

Study Sites (13)

Necmettin Erbakan University Meram Faculty of Medicine Hospital

Konya, Meram, 42080, Turkey (Türkiye)

Location

Bursa Uludağ University Hospital

Bursa, Nilüfer, 16059, Turkey (Türkiye)

Location

Karadeniz Technical University Hospital

Trabzon, Ortahisar, 61080, Turkey (Türkiye)

Location

Sakarya University Hospital

Sakarya, Serdivan, 54050, Turkey (Türkiye)

Location

Ankara Etlik City Hospital

Ankara, Yenimahalle, 06170, Turkey (Türkiye)

Location

Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital

Ankara, Yenimahalle, 06200, Turkey (Türkiye)

Location

Gazi University

Ankara, Yenimahalle, 06500, Turkey (Türkiye)

Location

Afyonkarahisar University of Health Sciences Hospital

Afyonkarahisar, 03030, Turkey (Türkiye)

Location

Ankara University Faculty of Medicine Hospital

Ankara, 06230, Turkey (Türkiye)

Location

Hacettepe University Faculty of Medicine Hospital

Ankara, 06230, Turkey (Türkiye)

Location

Dicle University Hospital

Diyarbakır, 21280, Turkey (Türkiye)

Location

Tekirdağ Namık Kemal University Hospital

Tekirdağ, 59100, Turkey (Türkiye)

Location

Van Yüzüncü Yıl University Dursun Odabaş Hospital

Van, 65080, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Gastrointestinal Stromal Tumors; Carcinoma, Hepatocellular

Interventions

Clobetasol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Liver Neoplasms; Liver Diseases

Intervention Hierarchy (Ancestors)

Betamethasone; Steroids, Fluorinated; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Ozan Yazıcı, Prof.

  Gazi University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: This study follows a parallel assignment model, where participants are assigned to one of three intervention groups based on the treating physician's decision. Each group receives a different preventive approach for regorafenib-induced hand-foot skin reaction (HFSR): 1. Oral zinc supplementation + transdermal clobetasol cream 2. Transdermal clobetasol cream alone 3. Oral zinc supplementation alone Participants will remain in their assigned groups throughout the study period, and no crossover between groups will occur. The study aims to compare the efficacy of these interventions in preventing and reducing the severity of HFSR.

Study Record Dates

• First Submitted: February 21, 2025
• First Posted: March 4, 2025
• Study Start: February 20, 2025
• Primary Completion: September 1, 2025
• Study Completion: September 7, 2025
• Last Updated: September 15, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

TU (13)