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

NCT05939726 | Completed

• 1 other identifier: CRC005-ECaPPE
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Palmar-Plantar Erythrodysesthesia; Palmar-Plantar Erythrodysesthesia Due to Cytotoxic Therapy

Keywords

Palmar-Plantar Erythrodysesthesia; Cytotoxic therapy; Capecitabine; Vitamin E; Tocotrienol; Tocopherol; Topical applications; Randomised controlled trial; Urea cream; Hand-foot syndrome; Supportive care

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Palmar-plantar erythrodysesthesia (PPE) worsening

  At Day 22, Day 43, Day 64, and Day 127 of cream treatment

• Time-to-PPE resolution

  At Day 22, Day 43, Day 64, and Day 127 of cream treatment

• Time-to-PPE worsening

  At Day 22, Day 43, Day 64, and Day 127 of cream treatment

• Dermatology Life Quality Index (0 - 30)

  At Day 22, Day 43, Day 64, and Day 127 of cream treatment

• Pain score (numerical scale of 1 to 10)

  At Day 22, Day 43, Day 64, and Day 127 of cream treatment

Study Arms (3)

Moisturising Cream with Vitamin E and Urea Cream

EXPERIMENTAL

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; Other: Urea cream

Moisturising Cream without Vitamin E and Urea Cream

EXPERIMENTAL

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; Other: Urea cream

Urea Cream Only

ACTIVE COMPARATOR

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

Interventions

Urea cream OTHER

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

Moisturising Cream with Vitamin E and Urea Cream; Moisturising Cream without Vitamin E and Urea Cream; Urea Cream Only

Moisturising cream with vitamin E concentrate OTHER

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.

Moisturising Cream with Vitamin E and Urea Cream

Moisturising cream without vitamin E concentrate OTHER

This moisturising cream is a similar moisturising cream but without the addition of the vitamin E concentrate

Moisturising Cream without Vitamin E and Urea Cream

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old and above
• Able to give written consent freely
• Receiving capecitabine 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sarawak General Hospital: lead
• Avantsar Sdn. Bhd.: collaborator
• Universiti Sains Malaysia: collaborator

Study Sites (1)

Sarawak General Hospital

Kuching, Sarawak, 93586, Malaysia

Location

Related Publications (12)

• Gressett SM, Stanford BL, Hardwicke F. Management of hand-foot syndrome induced by capecitabine. J Oncol Pharm Pract. 2006 Sep;12(3):131-41. doi: 10.1177/1078155206069242.

  PMID: 17022868 BACKGROUND

• Nikolaou V, Syrigos K, Saif MW. Incidence and implications of chemotherapy related hand-foot syndrome. Expert Opin Drug Saf. 2016 Dec;15(12):1625-1633. doi: 10.1080/14740338.2016.1238067. Epub 2016 Oct 8.

  PMID: 27718746 BACKGROUND

• Kwakman JJM, Elshot YS, Punt CJA, Koopman M. Management of cytotoxic chemotherapy-induced hand-foot syndrome. Oncol Rev. 2020 May 13;14(1):442. doi: 10.4081/oncol.2020.442. eCollection 2020 Feb 18.

  PMID: 32431787 BACKGROUND

• Lou Y, Wang Q, Zheng J, Hu H, Liu L, Hong D, Zeng S. Possible Pathways of Capecitabine-Induced Hand-Foot Syndrome. Chem Res Toxicol. 2016 Oct 17;29(10):1591-1601. doi: 10.1021/acs.chemrestox.6b00215. Epub 2016 Sep 28.

  PMID: 27631426 BACKGROUND

• Milano G, Etienne-Grimaldi MC, Mari M, Lassalle S, Formento JL, Francoual M, Lacour JP, Hofman P. Candidate mechanisms for capecitabine-related hand-foot syndrome. Br J Clin Pharmacol. 2008 Jul;66(1):88-95. doi: 10.1111/j.1365-2125.2008.03159.x. Epub 2008 Mar 13.

  PMID: 18341672 BACKGROUND

• Zhang RX, Wu XJ, Lu SX, Pan ZZ, Wan DS, Chen G. The effect of COX-2 inhibitor on capecitabine-induced hand-foot syndrome in patients with stage II/III colorectal cancer: a phase II randomized prospective study. J Cancer Res Clin Oncol. 2011 Jun;137(6):953-7. doi: 10.1007/s00432-010-0958-9. Epub 2010 Nov 27.

  PMID: 21113620 BACKGROUND

• Hofheinz RD, Gencer D, Schulz H, Stahl M, Hegewisch-Becker S, Loeffler LM, Kronawitter U, Bolz G, Potenberg J, Tauchert F, Al-Batran SE, Schneeweiss A. Mapisal Versus Urea Cream as Prophylaxis for Capecitabine-Associated Hand-Foot Syndrome: A Randomized Phase III Trial of the AIO Quality of Life Working Group. J Clin Oncol. 2015 Aug 1;33(22):2444-9. doi: 10.1200/JCO.2014.60.4587. Epub 2015 Jun 29.

  PMID: 26124485 BACKGROUND

• Wolf SL, Qin R, Menon SP, Rowland KM Jr, Thomas S, Delaune R, Christian D, Pajon ER Jr, Satele DV, Berenberg JL, Loprinzi CL; North Central Cancer Treatment Group Study N05C5. Placebo-controlled trial to determine the effectiveness of a urea/lactic acid-based topical keratolytic agent for prevention of capecitabine-induced hand-foot syndrome: North Central Cancer Treatment Group Study N05C5. J Clin Oncol. 2010 Dec 10;28(35):5182-7. doi: 10.1200/JCO.2010.31.1431. Epub 2010 Nov 8.

  PMID: 21060036 BACKGROUND

• Hoesly FJ, Baker SG, Gunawardane ND, Cotliar JA. Capecitabine-induced hand-foot syndrome complicated by pseudomonal superinfection resulting in bacterial sepsis and death: case report and review of the literature. Arch Dermatol. 2011 Dec;147(12):1418-23. doi: 10.1001/archdermatol.2011.320.

  PMID: 22184763 BACKGROUND

• Kara IO, Sahin B, Erkisi M. Palmar-plantar erythrodysesthesia due to docetaxel-capecitabine therapy is treated with vitamin E without dose reduction. Breast. 2006 Jun;15(3):414-24. doi: 10.1016/j.breast.2005.07.007. Epub 2005 Sep 26.

  PMID: 16188440 BACKGROUND

• Yamamoto D, Yamamoto C, Iwase S, Kuroda Y, Odagiri H, Nagumo Y. Efficacy of Vitamin E Treatment for Hand-Foot Syndrome in Patients Receiving Capecitabine. Breast Care (Basel). 2010;5(6):415-416. doi: 10.1159/000322660. Epub 2010 Nov 26. No abstract available.

  PMID: 21494409 BACKGROUND

• Bozkurt Duman B, Kara B, Oguz Kara I, Demiryurek H, Aksungur E. Hand-foot syndrome due to sorafenib in hepatocellular carcinoma treated with vitamin E without dose modification; a preliminary clinical study. J BUON. 2011 Oct-Dec;16(4):759-64.

  PMID: 22331734 BACKGROUND

MeSH Terms

Conditions

Hand-Foot Syndrome

Condition Hierarchy (Ancestors)

Drug Eruptions; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders

Study Officials

• Pei Jye Voon, M.D

  Sarawak General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The use of the investigational creams, i.e. moisturising creams with or without vitamin E concentrate will be double-blinded. Both creams will be the same in colour, texture, packaging, and labelling. The patients, investigators, and blinded study personnel will blinded the patients' assignment of the investigational creams. On the other hand, the use of urea cream will be open-labelled.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Oncologist

Study Record Dates

• First Submitted: June 25, 2023
• First Posted: July 11, 2023
• Study Start: May 16, 2023
• Primary Completion: May 22, 2025
• Study Completion: June 20, 2025
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

MY (1)