Trial of Moisturising Cream With/Without Vitamin E and Urea Cream or Urea Cream Alone in Palmar-Plantar Erythrodysesthesia (ECaPPE)

Trial of Moisturising Cream With/Without Vitamin E and Urea Cream or Urea Cream Alone in Palmar-Plantar Erythrodysesthesia

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)

This is a placebo-controlled, double-blind randomised controlled trial comparing the effects of a cosmetic moisturising cream containing palm-oil derived vitamin E concentrate and placebo (1:1) in addition to urea-based cream and standard of care in capecitabine-associated PPE of NCI-CTCAE grade 1 in patients who are receiving capecitabine monotherapy or in combination with other agent(s).

This is a placebo-controlled, double-blind randomised trial comparing a cosmetic moisturising cream containing palm-oil derived vitamin E concentrate and placebo (1:1) in addition to urea-based cream and the standard of care in treating capecitabine-associated PPE of NCI- CTCAE grade 1 in patients who are receiving capecitabine monotherapy or in combination with other agent(s). In this study, approximately 60 patients who had capecitabine-associated PPE of NCI-CTCAE grade 1 will be recruited and randomised to two study arms. They will need to use the creams on top of the standard of care for PPE at least two times a day daily for nine weeks or three treatment cycles of the capecitabine-based regime. The participants will be assessed for prevention of PPE worsening (primary efficacy endpoint), resolution of PPE, dermatology-related QoL, and pain score (secondary efficacy endpoints), as well as palm-oil- derived vitamin E cream's safety profile (safety endpoints) throughout the study period. After the completion of the nine-week study treatment, participants from both arms shall be continued with the current standard of care for PPE management.

Palmar-Plantar Erythrodysesthesia, Cytotoxic therapy, Capecitabine, Vitamin E, Tocotrienols, Tocopherols, Topical applications, randomised controlled trial, Treatment, Urea cream

There are three arms in this trial. The first two arms involving combination of moisturising creams and urea cream are double-blind. Both moisturising containing and not containing vitamin E will have identical weights, packaging, and colour. Study participants, investigators, and study personnel (blinded) will be blinded to the participants' assignment of the treatment arms. Unblinded study personnel will generate the randomisation schedule and perform the randomisation. However, the third arm is an open-label arm that involves only urea cream.

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.

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.

Participants who are randomised to this arm will receive only urea-based cream as the standard of care for PPE management. They will be required to use the urea cream at least twice a day.

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. Urea cream (10%w/w) is used as the standard of care for PPE.

This moisturising cream is a similar moisturising cream but without the addition of the vitamin E concentrate Urea cream (10%w/w) is used as the standard of care for PPE.

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.

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.

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 as PPE prophylaxis 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

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