SHIELD: Sorafenib Hand-foot Syndrome Inhibition With Pre-Emptive Local Delivery of Topical Indomethacin

NCT07560566 | Recruiting Phase 2

• 1 other identifier: 202508066MIPC
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

SHIELD is a single-center, open-label, single-arm prospective study designed to evaluate whether pre-emptive topical indomethacin can reduce sorafenib-associated hand-foot syndrome (HFS) in patients with advanced hepatocellular carcinoma (HCC). Eligible adult patients with advanced HCC who are planned to initiate sorafenib will receive standard sorafenib treatment together with prophylactic 1% topical indomethacin gel applied to both hands twice daily for up to 12 weeks, or until development of HFS or discontinuation of sorafenib, whichever occurs first. The primary endpoint is the incidence of all-grade HFS during the first 12 weeks of sorafenib treatment. Secondary endpoints include grade 2 or higher HFS rate, grade 3 or higher HFS rate, mean sorafenib dose intensity during the first 12 weeks, adverse events of special interest, and duration of sorafenib treatment. The study will enroll 39 patients and compare outcomes with historical control data.

Conditions

Hepato Cellular Carcinoma (HCC); Hand Foot Skin Syndrome

Keywords

hepatocellular carcinoma; Hand foot skin syndrome; Topical NSAID; Prophylaxis; Sorafenib

Outcome Measures

Primary Outcomes (1)

• All-grade hand-foot skin reaction rate during the first 12 weeks of sorafenib treatment

  The proportion of participants who experience any grade of hand-foot skin reaction during the first 12 weeks of sorafenib treatment. Hand-foot skin reaction severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. The grading scale ranges from Grade 1 to Grade 5, with higher grades indicating greater severity. For participants who discontinue sorafenib before Week 12, hand-foot skin reaction events will be assessed during the actual sorafenib treatment period.

  From initiation of sorafenib treatment through Week 12, assessed up to 12 weeks.

Secondary Outcomes (5)

• Grade ≥2 hand-foot skin reaction rate during the first 12 weeks

  From initiation of sorafenib treatment through Week 12, assessed up to 12 weeks.

• Grade ≥3 hand-foot skin reaction rate during the first 12 weeks

  From initiation of sorafenib treatment through Week 12, assessed up to 12 weeks.

• Mean sorafenib dose intensity during the first 12 weeks of treatment

  From initiation of sorafenib treatment through Week 12, assessed up to 12 weeks.

• Adverse events of special interest in the first 12 weeks of sorafenib treatment

  From initiation of sorafenib treatment through Week 12, assessed up to 12 weeks.

• Treatment duration of sorafenib

  From initiation of sorafenib treatment until permanent discontinuation of sorafenib, assessed up to 24 weeks.

Study Arms (1)

Experimental

EXPERIMENTAL

Prophylactic topical indomethacin

Drug: Topical Indomethacin

Interventions

Topical Indomethacin DRUG

The participant will be provided with 2 tubes (20 gm each) per week in the first 4 weeks (D1, 8, 15, 22), 4 tubes per 2 weeks at the second 4 weeks (D29, 43), and 4 tubes per 4 weeks for the third 4 weeks (D57) suffice for topical application over 12 weeks. The participant will apply 1 g (1 g = two fingertip units \[FTU\]: one FTU for one surface of one hand) of 1% topical indomethacin on the palmar and dorsal surface of each hand twice daily (= 4g/day) until discontinuation of sorafenib or 12 weeks or development of HFS, whichever is earlier. If the patient has adequate residual indomethacin gel at the visit, the prescribing amount may be reduced accordingly.

Experimental

Eligibility Criteria

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

You may qualify if:

• Female or male patients, 18 years of age or older, able to understand and give written informed consent.
• Hepatocellular carcinoma, diagnosed by clinical or pathological diagnosis.
• Patients with advanced HCC, defined as those with macrovascular invasion, extrahepatic spread, or who failed or are not feasible to locoregional therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Child-Pugh score A-B7.
• Sorafenib is deemed as an appropriate treatment option for the patient at the discretion of the investigator.
• Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in Appendices.
• Willing and able to comply with the requirements and restrictions in this protocol.

You may not qualify if:

• Exposure to multikinase inhibitors or capecitabine within 1 week before starting the study treatment.
• Unresolved HFS.
• Exposure to oral NSAID, topical NSAID, or topical steroid within 1 week before starting the study treatment.
• Known allergy to NSAID.
• Any concurrent systemic chemotherapy, immunotherapy, or biologic for cancer treatment.
• Recent gastrointestinal bleeding within 12 weeks.
• Female patients who are pregnant, breast-feeding, or male or female patients of reproductive potential who are not employing an effective method of birth control.
• Have other concurrent medical or psychiatric conditions that, in the investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
• Any medical condition that, in the investigator's or sponsor's opinion, poses an undue risk to the patient's participation in the study.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, 10002, Taiwan

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Indomethacin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Yu-Yun Shao, M.D., Ph.D.

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: May 1, 2026
• Study Start: December 9, 2025
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): April 30, 2029
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)