Efficacy and Safety of Moisturising Cream With or Without Vitamin E and Urea Cream in Palmar-plantar Erythrodysesthesia

Study Overview
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Brief Summary
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This is a single-centre, phase II, three-arm, randomised controlled trial to evaluate the efficacy and safety of a cosmetic moisturising cream containing palm-oil-derived vitamin E concentrate or a similar moisturising cream without the vitamin E concentrate in addition to urea-based cream, or urea-based cream alone (1:1:1) in patients who are receiving capecitabine-based cancer therapy and develop capecitabine-associated PPE of NCI-CTCAE grade 1.

Detailed Description
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In this study, 90 cancer patients from Sarawak General Hospital who are receiving capecitabine-based therapy (2000-2500mg daily dose) and develop PPE of NCI-CTCAE grade 1 will be recruited and randomised 1:1:1 to three study arms. The participants who are randomised to treatment arms will receive moisturising creams with or without palm-oil-derived vitamin E concentrate, in addition to urea-based cream for external application on palms and soles. Participants who are randomised to the control arm will be required to use urea-based cream only. Both patients and investigators will be blinded to the investigational cream assignment i.e., double-blind. However, blinding will not be applicable to the use of urea cream i.e., open-label. The patients will need to use the cream(s) at least two times a day for nine to eighteen weeks or equivalent to three to six treatment cycles of capecitabine. At week-9, the patients who are planned to continue capecitabine therapy and do not develop PPE of grade 2/3 will continue to receive the study treatments for additional nine weeks or equivalent to three treatment cycles of capecitabine (extended period). The patients will be assessed for their PPE grading, symptoms, dermatological quality of life, pain score, and adverse events at the end of each capecitabine treatment cycle at the clinic.

Official Title
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A Phase II, Randomised Controlled Trial to Evaluate the Efficacy and Safety of Moisturising Creams With or Without Palm-oil-derived Vitamin E Concentrate in Addition to Urea-based Cream or Urea-based Cream Alone in Capecitabine-associated Palmar-Plantar Erythrodysesthesia (ECaPPE)

Conditions
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Palmar-Plantar Erythrodysesthesia, Palmar-Plantar Erythrodysesthesia Due to Cytotoxic Therapy

Intervention / Treatment
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* Other: Moisturising cream with vitamin E concentrate
* Other: Moisturising cream without vitamin E concentrate
* Other: Urea cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years old and above Able to give written consent freely Receiving capecitabine at 2000-2500mg/m2/day or 1000-1250/m2/dose twice a day, at least 1 dose, as monotherapy or in combination therapy Receiving urea-based cream Developed PPE of NCI-CTCAE grade 1 Have at least three cycles of chemotherapy to complete Life expectancy ≥ 6 months ECOG≤2 Exclusion Criteria: Unable to understand the information sheet and informed consent form Allergy history towards vitamin E and its isoforms or any components of the investigational products Unable to tolerate urea-based products Other pre-existing dermatological diseases or conditions that may interfere the evaluation of PPE PPE complicated with infection Receiving other agent(s) that are known to cause PPE or hand- foot syndrome and hand-foot skin reactions Receiving long-term topical or systemic steroid treatment (except as part of pre-or post-medications of chemotherapy regime) Pregnant or lactating mother Participating in another interventional trial Refuses to interrupt his/her usual care Anticipated inability to follow-up

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Moisturising Cream with Vitamin E and Urea Cream<br>Participants who are randomised in this arm will receive a moisturising cream containing palm-oil-derived vitamin E concentrate for external application on both palms and soles, in addition to urea-based cream as the standard of care for PPE management. They will be required to apply the investigational cream first, followed by the urea-based cream, at least two times a day. | Other: Moisturising cream with vitamin E concentrate<br>* The vitamin E moisturising cream contains 3% w/w of palm-oil-derived vitamin E concentrate, consisting of the following isomers: alpha-tocopherol, alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol, and delta-tocotrienol. This formula provides a total of 1.2g tocotrienols per 100g product.<br>Other: Urea cream<br>* Urea cream (10%w/w) is used as the standard of care for PPE.<br>|
| Experimental: Moisturising Cream without Vitamin E and Urea Cream<br>Participants who are randomised to this arm will receive a basic or plain moisturising cream without Vitamin E for external application on both palms and soles, in addition to urea-based cream as the standard of care for PPE management. They will be required to apply the investigational cream first, followed by the urea-based cream, at least two times a day. | Other: Moisturising cream without vitamin E concentrate<br>* This moisturising cream is a similar moisturising cream but without the addition of the vitamin E concentrate<br>Other: Urea cream<br>* Urea cream (10%w/w) is used as the standard of care for PPE.<br>|
| Active Comparator: Urea Cream Only<br>Participants who are randomised to this arm will receive urea-based cream only as the standard of care for PPE management. They will be required to use the urea cream at least twice a day. | Other: Urea cream<br>* Urea cream (10%w/w) is used as the standard of care for PPE.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Palmar-plantar erythrodysesthesia (PPE) resolution | Number of participants who have resolved PPE (NCI-CTCAE grade 1 to 0) | At Day 22, Day 43, Day 64, and Day 127 of cream treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Palmar-plantar erythrodysesthesia (PPE) worsening | Number of participants who have worsened PPE (NCI-CTCAE grade 1 to 2/3) | At Day 22, Day 43, Day 64, and Day 127 of cream treatment | 
| Time-to-PPE resolution | Time-to-PPE resolution via patient self-reported symptoms in standardised diary | At Day 22, Day 43, Day 64, and Day 127 of cream treatment | 
| Time-to-PPE worsening | Time-to-PPE worsening via patient self-reported symptoms in standardised diary | At Day 22, Day 43, Day 64, and Day 127 of cream treatment | 
| Dermatology Life Quality Index (0 - 30) | The Dermatology Life Quality Index (DLQI) consists of 10 questions, and each question is assigned a score (0 to 3). The total score ranges from 0 to 30, with higher scores indicating greater impairment in the individual's quality of life. | At Day 22, Day 43, Day 64, and Day 127 of cream treatment | 
| Pain score (numerical scale of 1 to 10) | The pain score is assessed using a 1-10 numeric rating pain scale, where 1 represents no pain at all, and 10 is the worst pain. | At Day 22, Day 43, Day 64, and Day 127 of cream treatment | 
| Overall adverse events | Frequency of overall adverse events | At Day 22, Day 43, Day 64, and Day 127 of cream treatment | 
| Dermatology-related adverse events | Frequency of dermatology-related adverse events | At Day 22, Day 43, Day 64, and Day 127 of cream treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Palmar-Plantar Erythrodysesthesia, Cytotoxic therapy, Capecitabine, Vitamin E, Tocotrienol, Tocopherol, Topical applications, Randomised controlled trial, Urea cream, Hand-foot syndrome, Supportive care