Clinical trial NCT04568330: Prevention of Hand-foot Skin Reaction
Official title: Re-validating Prophylactic Efficacy of Urea-based Cream on Sorafenib-induced Hand-foot Skin Reaction in Patients With Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hepatocellular Carcinoma
Keywords: hand-foot skin reaction
side effect of sorafenib
symptom related to target therapy
efficacy of urea-based cream
symptom management
Lead sponsor: Taipei Veterans General Hospital, Taiwan
Sponsor class: OTHER_GOV
First posted: 2020-09-29
Enrollment: 129
Sex: ALL
Minimum age (years): 54
Maximum age (years): 91
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Sorafenib-induced hand-foot skin reaction (HFSR) is a dose-dependent side effect in patients with advance hepatocellular carcinoma (HCC). The appropriate prophylactic dose of urea-based cream and comparison of its effectiveness with other creams remain unclear. The aim of this study was re-validating the prophylactic HFSR incidence density and cutaneous wetness of 10% urea-based cream on sorafenib-induced HFSR in patients with advanced HCC.

Detailed description: Methods

Patients

This study population consisted of patients with (1) HCC by proof of pathology, (2) presence of tumor thrombus in the main trunk of the portal vein or the first-order branches of the portal vein with minimal ascetics or with no ascetics by abdominal CT scan, (3) Child-Pugh liver function class A, (4) planning to receive oral sorafenib 400 mg twice per day, (5) age of 20 or more years old, and (6) able to communication in Chinese, Taiwanese or Hakka. Patients with (1) encephalopathy, psychosis, cognition impairment, blindness or hearing impairment, (2) allergic history to urea, (3) present ulceration, blisters, infective problems on the palms or soles, or (4) previous surgery, systematic chemotherapy or frequent radial ablation were excluded.

Research procedure

This is a randomized double-blind experiment study. Sample size was estimated by the G. power software version 3.1, which was set with logistic regression, odds ratio: 3.8, and power: 0.80. The estimated sample size should be 125 at least. This study, there was recruited 129 patients (43 patients in each groups). All eligible patients were recruited from Taipei Veterans General Hospital between January 1st and December 31th, 2014. They were randomly assigned in a ratio of 1:1:1 to treat with best supportive care plus moisturizing cream (A group), BSC plus 10% urea-based cream (B group) and BSC alone (group C which is comparison group),by method of EXCEL random sampling. A case manager recruited the eligible patients who also conducted informed consent and patient education. A research employee had responsibilities to record patients' demographic data, provide non-label cream and check previous container of the cream that should be exhausted. A medical oncologist or a nurse had responsibilities to assess patients' severity of HFSR and cutaneous wetness. The assessment was done on 3 days before starting sorafenib treatment and each 7 days after the starting, total 9 times. Creams were provided after the assessment. When patients developed HFSR, they will be referred to receive the most appropriate management.

Interventions

Interventions for group C (comparison group) who received BSC alone were (1) informed of potential presentations of HFSR, (2) asked for wearing waterproof gloves before execute household or work with water, (3) provided the method of contacting with healthcare specialists for confirming early diagnosis of HFSR, and (4) asked for self-report when they occurred symptoms of HFSR. The A group with BCS plus moisturizing cream received the interventions as the comparison group, was given the moisturizing cream (dimethicone, fragrance free, Aveeno, United States) for 9 times and was instructed how to use the cream. The education of usage included (1) using the cream twice a day from 3 days before starting sorafenib and each week post starting sorafenib, (2) scooping out nut-sized cream with a unique spoon each time, (3) gently applied the cream evenly on symmetrical palms below wrists and symmetrical soles below ankles each time, (4) wore unique cotton gloves immediately after the appalment of cream for 30 minutes each time. A B group with BCS plus 10% urea-based cream had the similar interventions as the A group with BCS plus moisturizing cream except being given the cream container with different component (10% urea; Sipharr, Taiwan). The outlook of the containers with the two kinds of cream was the same. All the cream looks white and grey.

Outcomes and assessment

Data of con founders and two end-points, incidence density of HFSR and cutaneous wetness, were collected. The con-founders included gender, age, numbers of chronic illnesses, numbers of metastatic regions as well as levels of white count, hemoglobin, bleeding time, liver enzymes, albumin and electrolyte.

The grades of HFSR were assessed by NCI-CTCAE version 4, which was developed by Dueck et al. This is an available psychometric patient-reported instrument. Body water with 33% or less meant dry skin, 34% to 37% meant mild dry skin, 38% to 42% meant general status, 43% to 46/% was mild moisty skin and 47% or more presented moisty skin. When using the scanner, examiners had to confirm whether it tied to fix on the skin.

Ethical considerations

This study was approved by the Institution Review Board of the Taipei Veterans General Hospital (2013-13-009B). Informed consent was obtained from all patients by a case manager on 3 days before starting sorafenib. Patients were explained the study protocol and were educated self-care skills by the case manager. All of them were well aware that their rights will be protected, the risk of participation will be limited to the lowest and most suitable management will be arranged when they developed sorafenib-induced HFSR.

Eligibility criteria: Inclusion Criteria:

* HCC by proof of pathology
* Presence of tumor thrombus in the main trunk of the portal vein or the first-order branches of the portal vein with minimal ascetics or with no ascetics by abdominal CT scan
* Child-Pugh liver function class A
* Planning to receive oral sorafenib 400 mg twice per day
* Age of 20 or more years old
* Able to communication in Chinese, Taiwanese or Hakka

Exclusion Criteria:

* Encephalopathy, psychosis, cognition impairment, blindness or hearing impairment
* Allergic history to urea
* Present ulceration, blisters, infective problems on the palms or soles
* Previous surgery, systematic chemotherapy or frequent radial ablation

Primary outcomes:
measure: Scale
timeFrame: three days before taking Sorafenib
Secondary outcomes:
measure: Scale
timeFrame: 1 week after taking Sorafenib
Other outcomes:
measure: Scale
timeFrame: 2 week after taking Sorafenib
measure: Scale
timeFrame: 3 week after taking Sorafenib
measure: Scale
timeFrame: 4 week after taking Sorafenib
measure: Scale
timeFrame: 5 week after taking Sorafenib
measure: Scale
timeFrame: 6 week after taking Sorafenib
measure: Scale
timeFrame: 7 week after taking Sorafenib
measure: Scale
timeFrame: 8 week after taking Sorafenib
Locations:
Study officials:
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