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The Effect of Urea Cream on Sorafenib-associated Hand-Foot Skin Reaction

Phase 4
Completed
Conditions
Hepatocellular Carcinoma
Interventions
Drug: Urea Cream 20%
Drug: Placebos
Registration Number
NCT03212625
Lead Sponsor
Korea University Guro Hospital
Brief Summary

Many investigators have studied for prevention and care of Hand-Foot Skin Reaction(HFSR), and urea cream is typical representative. Recent study was performed prevention effect of urea cream for Hand-Foot Skin Reaction(HFSR) on 871 Chinese. But the study did not designed as placebo-control group and it had big defect in double-blinded.

Therefore, it needs complementary study as double-blinded placebo-controlled trial and effect of urea cream on Korean patient group.

Detailed Description

Sorafenib is multiple tyrosine kinase inhibitor. It blocks path that such as Raf-1, Vascular Endothelial Growth Factor Receptor (VEGFR), Platelet-Drived Growth Factor Receptor-β (PDGFR-β), c-Jit, Flt-3. Sorafenib was known to increase life rate about processed hepatocellular carcinoma. So it is advised as standard treatment for liver cancer patient who has processed Barcelona Clinic Liver Cancer (BCLC) disease period C.

Sorafenib related side effect has reported such as fatigue, diarrhea, vomit, nausea, pruritus, depilation, Hand-Foot Skin Reaction(HFSR). Among the symptoms, Hand-Foot Skin Reaction(HFSR) is the most occurrence after using sorafenib and major reason of drug dose de-escalation, it function as decrease anti-cancer effect of sorafenib. It is known for the reason of Hand-Foot Skin Reaction(HFSR) occurrence is caused by tyrosine kinase inhibitive action, and its characteristic symptom is known as keratocyte necrosis, dermal edema, parakeratosis, hyperkeratosis. The level is categorized grade 1,2,3 according to the severity.

The result of meta-analysis of 24 clinical trials that contained 6000 patients, Hand-Foot Skin Reaction(HFSR) occured 39% of sorafenib used patients and 9% of total patients had grade 3 Hand-Foot Skin Reaction(HFSR). But prevalence rate on hepatocellular carcinoma patients who used sorafenib is about 51% on Japanese, 45% on Asia-pacific patient (inclusive Korean) and 73.6% on Chinese. Prevalence rate of Hand-Foot Skin Reaction(HFSR) is different from result of each study, but about 50% of sorafenib used patients has had Hand-Foot Skin Reaction(HFSR) generally and Asian has more higher degree of prevalence rate. Therefore, prevent and care of Hand-Foot Skin Reaction(HFSR) on Korean hepatocellular carcinoma patients who used sorafenib is required.

Urea cream is typical representative for prevention and care of Hand-Foot Skin Reaction(HFSR). As stability-guaranteed drug, it is relatively cheap, locally affect and has used for psoriasis treatment. Also it is known for curative effacement on Hand-Foot Skin Reaction(HFSR) after use tyrosine kinase inhibitor such as sorafenib, sunitinib.

Therefore, it needs complementary study as double-blinded placebo-controlled trial and effect of urea cream on Korean patient group.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
288
Inclusion Criteria
  • Patient who was diagnosed with hepatocellular carcinoma, and was accompanied by impossible for radical treatment in disease period or do not reaction for local treatment, and the first time for sorafenib injection.

  • Standard of hepatocellular carcinoma diagnosis (2014, The Korean Liver Cancer Association)

    1. Suitable on hepatocellular carcinoma pathologically
    2. Hepatic nodule size over 1 cm on high-risk patients(hepatitis B virus positive, hepatitis C virus positive and liver cirrhosis) that identified by ultrasonography : In the case of suitable on hepatocellular carcinoma on over in one or two more dynamic contrast enhanced CT, dynamic contrast enhanced MRI, or MRI with Gadolinium Ethoxybenzyl Diethylenetriamine Pentaacetic Acid(Gd-EOB-DTPA)
    3. Hepatic nodule size under 1 cm on high-risk patients that identified by ultrasonography : serum Alpha-fetoprotein(AFP) elevated over normal range constantly when hepatitis activity was restrained, and the case of suitable on hepatocellular carcinoma on over in two more the above image diagnoses
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Exclusion Criteria
  • Unsuitable on inclusion criteria
  • Patient who has had systemic anticancer therapy before (including sorafenib)
  • Patient who is receiving another treatment to hepatocellular carcinoma recent 3 weeks (allow to local treatment of metastasis lesion only)
  • Pregnant or Breastfeeding
  • Urea cream contraindication patient (Acute eczema, Inflammatory dermatopathy and Hypersensitivity on Urea and Methylparaben)
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Urea cream 20%Urea Cream 20%144 patients spread urea cream (urea 20%)
PlaceboPlacebos144 patients spread placebo cream (urea 0%)
Primary Outcome Measures
NameTimeMethod
Cumulative incidence of Hand-Foot Skin Reaction(HFSR) on each group12 weeks treatment

Comparison of cumulative incidence of HFSR between placebo group and urea cream group

Secondary Outcome Measures
NameTimeMethod
Assessment of Quality Of Life (QOL)12 weeks treatment

Assessment of QOL related to HFSR using The Hand-Foot Skin Reaction and Quality of Life Questionnaire (HF-QoL) scoring system. HF-QOL instrument comprises a 20-item symptom scale and an 18-item daily activity scale. Each item was scored from 0 (not at all) to 4 (always or extremely). Therefore, the range of score for HF-QoL was from 0 to 152 points. (Ref. Anderson et al. The Oncoligist 2015;20:831-838)

Incidence of HFSR on 2, 4, 8, and 12 weeks on each group2, 4, 8, and 12 weeks

Comparison of incidence of HFSR on 2, 4, 8, and 12 weeks between placebo group and urea cream group

Cumulative incidence of severe HFSR on each group12 weeks treatment

Comparison of cumulative incidence of severe HFSR (grade 2 or grade 3) between placebo group and urea cream group

Incidence of dose reduction or discontinuation of sorafenib due to HFSR on each group12 weeks treatment

Comparison of incidence of dose reduction or discontinuation of sorafenib due to HFSR on each group

Overall survival12 weeks treatment

Overall survival of patients

Tumor response12 weeks treatment

Tumor response using mRECIST criteria

Other side effect12 weeks treatment

The occurrence rate of other side effect excluding HFSR

Trial Locations

Locations (1)

Korea University Guro Hospital

🇰🇷

Seoul, Korea, Republic of

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