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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03212625
Recruitment Status : Completed
First Posted : July 11, 2017
Last Update Posted : August 22, 2019
Sponsor:
Collaborator:
Hanmi Pharmaceutical Company Limited
Information provided by (Responsible Party):
Ji Hoon Kim, 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.


Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: Urea Cream 20% Drug: Placebos Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 288 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 28, 2016
Actual Primary Completion Date : September 20, 2018
Actual Study Completion Date : September 20, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Foot Health

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 Name: Urea group

Placebo Comparator: Placebo
144 patients spread placebo cream (urea 0%)
Drug: Placebos
Sorafenib 400mg (twice daily), Spread placebo cream (urea 0%)
Other Name: Placebo group




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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)

  4. Overall survival [ Time Frame: 12 weeks treatment ]
    Overall survival of patients

  5. Tumor response [ Time Frame: 12 weeks treatment ]
    Tumor response using mRECIST criteria

  6. Other side effect [ Time Frame: 12 weeks treatment ]
    The occurrence rate of other side effect excluding HFSR

  7. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03212625


Locations
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Korea, Republic of
Korea University Guro Hospital
Seoul, Korea, Republic of, 08308
Sponsors and Collaborators
Korea University Guro Hospital
Hanmi Pharmaceutical Company Limited
Investigators
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Principal Investigator: Ji Hoon Kim, MD Associate Professor

Publications:

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Responsible Party: Ji Hoon Kim, Associate professor, Korea University Guro Hospital
ClinicalTrials.gov Identifier: NCT03212625    
Other Study ID Numbers: KUGH15337
First Posted: July 11, 2017    Key Record Dates
Last Update Posted: August 22, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ji Hoon Kim, Korea University Guro Hospital:
Urea Cream
Sorafenib
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Carbamide Peroxide
Sorafenib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Local
Anti-Infective Agents