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

Phase 2RecruitingNCT07560566

National Taiwan University Hospital39 enrolled

Overview

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.

This is a single-center, open-label, single-arm prospective study evaluating the prophylactic use of topical indomethacin for prevention of sorafenib-associated hand-foot syndrome (HFS) in patients with advanced hepatocellular carcinoma (HCC). Sorafenib is an established systemic treatment option for advanced HCC, but HFS is a frequent toxicity that may reduce quality of life and interfere with treatment delivery. Historical studies have reported all-grade HFS rates of approximately 45% in patients treated with sorafenib. Topical NSAIDs have shown preventive activity against chemotherapy-related HFS in prior studies. Based on this rationale, this study will investigate whether pre-emptive administration of 1% topical indomethacin gel can reduce the incidence of sorafenib-related HFS while avoiding the systemic adverse effects associated with oral NSAIDs. Eligible adult patients with advanced HCC who are planned to start sorafenib will receive sorafenib at an initial dose of 400 mg orally twice daily, with subsequent dose modification according to routine clinical practice. Participants will also apply 1% topical indomethacin gel to the palmar and dorsal surfaces of both hands twice daily (total 4 g/day) 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, defined according to NCI CTCAE version 5.0. Secondary endpoints include the incidence of grade 2 or higher HFS, incidence of grade 3 or higher HFS, mean sorafenib dose intensity during the first 12 weeks, adverse events of special interest, and sorafenib treatment duration. A total of 39 patients will be enrolled. Outcomes will be interpreted against historical control data.

Interventions

Topical IndomethacinDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Female or male patients, 18 years of age or older, able to understand and give written informed consent. 2. Hepatocellular carcinoma, diagnosed by clinical or pathological diagnosis. 3. Patients with advanced HCC, defined as those with macrovascular invasion, extrahepatic spread, or who failed or are not feasible to locoregional therapy. 4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 5. Child-Pugh score A-B7. 6. Sorafenib is deemed as an appropriate treatment option for the patient at the discretion of the investigator. 7. 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. 8. Willing and able to comply with the requirements and restrictions in this protocol. Exclusion Criteria: 1. Exposure to multikinase inhibitors or capecitabine within 1 week before starting the study treatment. 2. Unresolved HFS. 3. Exposure to oral NSAID, topical NSAID, or topical steroid within 1 week before starting the study treatment. 4. Known allergy to NSAID. 5. Any concurrent systemic chemotherapy, immunotherapy, or biologic for cancer treatment. 6. Recent gastrointestinal bleeding within 12 weeks. 7. 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. 8. 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. 9. Any medical condition that, in the investigator's or sponsor's opinion, poses an undue risk to the patient's participation in the study.

Outcomes

Primary Outcomes

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.