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

August 21, 2019 updated by: Ji Hoon Kim, Korea University Guro Hospital

The Effect of Urea Cream on Sorafenib-associated Hand-Foot Skin Reaction in Patients With Korean Hepatocellular Carcinoma Patients: Multicenter, Prospective Randomized Double-Blind Controlled Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

288

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Urea cream 20%
144 patients spread urea cream (urea 20%)
Drug: Urea Cream 20%
Sorafenib 400mg (twice daily), Spread urea cream (urea 20%)
Other Names:
  • Urea group
PLACEBO_COMPARATOR: Placebo
144 patients spread placebo cream (urea 0%)
Drug: Placebos
Sorafenib 400mg (twice daily), Spread placebo cream (urea 0%)
Other Names:
  • Placebo group

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative incidence of Hand-Foot Skin Reaction(HFSR) on each group
Time Frame: 12 weeks treatment
Comparison of cumulative incidence of HFSR between placebo group and urea cream group
12 weeks treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative incidence of severe HFSR on each group
Time Frame: 12 weeks treatment
Comparison of cumulative incidence of severe HFSR (grade 2 or grade 3) between placebo group and urea cream group
12 weeks treatment
Incidence of dose reduction or discontinuation of sorafenib due to HFSR on each group
Time Frame: 12 weeks treatment
Comparison of incidence of dose reduction or discontinuation of sorafenib due to HFSR on each group
12 weeks treatment
Assessment of Quality Of Life (QOL)
Time Frame: 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)
12 weeks treatment
Overall survival
Time Frame: 12 weeks treatment
Overall survival of patients
12 weeks treatment
Tumor response
Time Frame: 12 weeks treatment
Tumor response using mRECIST criteria
12 weeks treatment
Other side effect
Time Frame: 12 weeks treatment
The occurrence rate of other side effect excluding HFSR
12 weeks treatment
Incidence of HFSR on 2, 4, 8, and 12 weeks on each group
Time Frame: 2, 4, 8, and 12 weeks
Comparison of incidence of HFSR on 2, 4, 8, and 12 weeks between placebo group and urea cream group
2, 4, 8, and 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Korea University Guro Hospital

Collaborators

Hanmi Pharmaceutical Company Limited

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 28, 2016

Primary Completion (ACTUAL)

September 20, 2018

Study Completion (ACTUAL)

September 20, 2018

Study Registration Dates

First Submitted

July 2, 2017

First Submitted That Met QC Criteria

July 7, 2017

First Posted (ACTUAL)

July 11, 2017

Study Record Updates

Last Update Posted (ACTUAL)

August 22, 2019

Last Update Submitted That Met QC Criteria

August 21, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KUGH15337

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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