Hand-Foot Skin Reaction (HFSR)ZINCLO-HANDNCT06856590
ZINCLO-HAND: Zinc and Clobetasol for the Prevention of Regorafenib-Induced Hand-Foot Skin Reaction
A study testing Zinc Supplementation and Clobetasol Propionate 0.05% Cream in people with Hand-Foot Skin Reaction (HFSR), run by Gazi University at 13 sites in Turkey (Türkiye).
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hand-Foot Skin Reaction (HFSR)
- What is being tested?
- Zinc Supplementation and Clobetasol Propionate 0.05% Cream
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 13 sitesTurkey (Türkiye)
- Study dates
- 20 Feb 2025to 7 Sep 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 9Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Turkey (Türkiye)13 sites
Afyonkarahisar University of Health Sciences Hospital
Afyonkarahisar, 03030
Ankara Etlik City Hospital
Ankara, Yenimahalle, 06170
Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital
Ankara, Yenimahalle, 06200
Gazi University
Ankara, Yenimahalle, 06500
Ankara University Faculty of Medicine Hospital
Ankara, 06230
Hacettepe University Faculty of Medicine Hospital
Ankara, 06230
Bursa Uludağ University Hospital
Bursa, Nilüfer, 16059
Dicle University Hospital
Diyarbakır, 21280
Necmettin Erbakan University Meram Faculty of Medicine Hospital
Konya, Meram, 42080
Sakarya University Hospital
Sakarya, Serdivan, 54050
Tekirdağ Namık Kemal University Hospital
Tekirdağ, 59100
Karadeniz Technical University Hospital
Trabzon, Ortahisar, 61080
Van Yüzüncü Yıl University Dursun Odabaş Hospital
Van, 65080
About this study
Official title: Impact of Zinc Supplementation and Transdermal Clobetasol in the Prophylaxis of Regorafenib-Induced Hand-Foot Skin Reaction: A Prospective Non-Randomized Study
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.
Read more
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.
Read the 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.
- Conditions
- Hand-Foot Skin Reaction (HFSR)
- Being tested
- Zinc Supplementation, Clobetasol Propionate 0.05% Cream
- Keywords
- Regorafenib-Induced Skin Toxicity, Clobetasol, Zinc Supplementation, Metastatic Colorectal Cancer (mCRC), Gastrointestinal Stromal Tumor (GIST), Hepatocellular Carcinoma (HCC)
- Medical subject headings
- Colorectal Neoplasms, Gastrointestinal Stromal Tumors, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zinc SupplementationDietary 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).
Clobetasol Propionate 0.05% CreamDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. Receives: 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. Receives: Dietary Supplement: Zinc Supplementation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 8 weeks
Secondary outcomes (5)
Duration of Hand-Foot Skin Reaction (HFSR)
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.
Measured: 8 weeks
Regorafenib Dose Modifications Due to HFSR
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.
Measured: 8 weeks
Quality of Life (FACT-G Score Change)
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.
Measured: Baseline and 8 weeks
Progression-Free Survival (PFS) in Patients with and without Severe HFSR
The time from the start of regorafenib treatment to disease progression or death from any cause, whichever occurs first.
Measured: Up to 6 months
Overall Survival (OS) in Patients with and without Severe HFSR
The time from the start of regorafenib treatment to death from any cause.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2025
- Study start20 Feb 2025
- Primary completion1 Sep 2025
- Study completion7 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hand-Foot Skin Reaction (HFSR)Studies of the same condition, open and under way.
- More trials run by Gazi UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gazi University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Orhun Akdoğan, Gazi University
- Investigators
- Ozan Yazıcı, Prof., Study chair, Gazi University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06856590
- Sponsor's protocol ID
- AESH-EK-2025-042
- Other IDs
- Ankara Etlik City Hospital EC
- Acronym
- ZINCLO-HAND
- Status last verified
- Feb 2025
- First submitted
- 21 Feb 2025
- Last updated
- 15 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) will not be shared due to privacy regulations and institutional policies. Data access is restricted to the study team and authorized personnel to ensure compliance with ethical guidelines and patient confidentiality
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Zinc Supplementation and Transdermal Clobetasol in the Prophylaxis of Regorafenib-Induced Hand-Foot Skin Reaction: A Prospective Non-Randomized Study
- ClinicalTrials.gov ID
- NCT06856590
- Acronym / sponsor ID
- ZINCLO-HAND / AESH-EK-2025-042
- 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)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Gazi UniversityUniversity, hospital or other
- Study start
- 20 Feb 2025 (actual)
- Primary completion
- 1 Sep 2025 (actual)
- Study completion
- 7 Sep 2025 (actual)
- First posted
- 4 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- 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.
| Arm | Type | Receives |
|---|---|---|
| Zinc + Clobetasol Group | Experimental | Dietary Supplement: Zinc Supplementation, Drug: Clobetasol Propionate 0.05% CreamParticipants 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 | Experimental | Drug: Clobetasol Propionate 0.05% CreamParticipants 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 | Experimental | Dietary Supplement: Zinc SupplementationParticipants 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zinc SupplementationParticipants 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). | Dietary supplement | Zinc + Clobetasol Group, Zinc Alone |
| Clobetasol Propionate 0.05% CreamParticipants 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. | Drug | Clobetasol Alone Group, Zinc + Clobetasol Group |
Primary outcome
Incidence and Severity of Hand-Foot Skin Reaction (HFSR) at Week 8
Time frame: 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.
5 secondary outcomes
Duration of Hand-Foot Skin Reaction (HFSR)
Time frame: 8 weeks
Regorafenib Dose Modifications Due to HFSR
Time frame: 8 weeks
Quality of Life (FACT-G Score Change)
Time frame: Baseline and 8 weeks
Progression-Free Survival (PFS) in Patients with and without Severe HFSR
Time frame: Up to 6 months
Overall Survival (OS) in Patients with and without Severe HFSR
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2025.
- Individual participant dataSharing planned: No. Individual participant data (IPD) will not be shared due to privacy regulations and institutional policies. Data access is restricted to the study team and authorized personnel to ensure compliance with ethical guidelines and patient confidentiality
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ozan Yazıcı, Prof. study chair
Gazi University
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Zinc Supplementation and Clobetasol Propionate 0.05% Cream in people with Hand-Foot Skin Reaction (HFSR), run by Gazi University at 13 sites in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and Severity of Hand-Foot Skin Reaction (HFSR) at Week 8 (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2025.