Clinical trial NCT06856590: ZINCLO-HAND: Zinc and Clobetasol for the Prevention of Regorafenib-Induced Hand-Foot Skin Reaction
Official title: Impact of Zinc Supplementation and Transdermal Clobetasol in the Prophylaxis of Regorafenib-Induced Hand-Foot Skin Reaction: A Prospective Non-Randomized Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
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)
Lead sponsor: Gazi University
Sponsor class: OTHER
First posted: 2025-03-04
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence and Severity of Hand-Foot Skin Reaction (HFSR) at Week 8
timeFrame: 8 weeks
Secondary outcomes:
measure: Duration of Hand-Foot Skin Reaction (HFSR)
timeFrame: 8 weeks
measure: Regorafenib Dose Modifications Due to HFSR
timeFrame: 8 weeks
measure: Quality of Life (FACT-G Score Change)
timeFrame: Baseline and 8 weeks
measure: Progression-Free Survival (PFS) in Patients with and without Severe HFSR
timeFrame: Up to 6 months
measure: Overall Survival (OS) in Patients with and without Severe HFSR
timeFrame: 6 months
Other outcomes:
Locations:
city: Konya
country: Turkey
facility: Necmettin Erbakan University Meram Faculty of Medicine Hospital
state: Meram
city: Bursa
country: Turkey
facility: Bursa Uludağ University Hospital
state: Nilüfer
city: Trabzon
country: Turkey
facility: Karadeniz Technical University Hospital
state: Ortahisar
city: Sakarya
country: Turkey
facility: Sakarya University Hospital
state: Serdivan
city: Ankara
country: Turkey
facility: Ankara Etlik City Hospital
state: Yenimahalle
city: Ankara
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital
state: Yenimahalle
city: Ankara
country: Turkey
facility: Gazi University
state: Yenimahalle
city: Afyonkarahisar
country: Turkey
facility: Afyonkarahisar University of Health Sciences Hospital
city: Ankara
country: Turkey
facility: Ankara University Faculty of Medicine Hospital
city: Ankara
country: Turkey
facility: Hacettepe University Faculty of Medicine Hospital
city: Diyarbakır
country: Turkey
facility: Dicle University Hospital
city: Tekirdag
country: Turkey
facility: Tekirdağ Namık Kemal University Hospital
city: Van
country: Turkey
facility: Van Yüzüncü Yıl University Dursun Odabaş Hospital
Study officials:
affiliation: Gazi University
name: Ozan Yazıcı, Prof.
role: STUDY_CHAIR
References: