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

Palmar-Plantar Erythrodysesthesia Clinical Trial

— ECaPPE  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05939726
• Other study ID #: CRC005-ECaPPE
• Status: Recruiting
• Phase: N/A
• Start date: May 16, 2023
• Est. completion date: August 31, 2024

Study information

• Verified date: November 2023
• Source: Sarawak General Hospital
• Contact: Teck Long King, BPharm(Hons)
• Phone: 60168911615
• Email: kingtl[@]crc.moh.gov.my
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: August 31, 2024
• Est. primary completion date: August 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 18 years old and above

2. Able to give written consent freely

3. 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

4. Receiving urea-based cream

5. Developed PPE of NCI-CTCAE grade 1

6. Have at least three cycles of chemotherapy to complete

7. Life expectancy = 6 months

8. ECOG=2

Exclusion Criteria:

1. Unable to understand the information sheet and informed consent form

2. Allergy history towards vitamin E and its isoforms or any components of the investigational products

3. Unable to tolerate urea-based products

4. Other pre-existing dermatological diseases or conditions that may interfere the evaluation of PPE

5. PPE complicated with infection

6. Receiving other agent(s) that are known to cause PPE or hand- foot syndrome and hand-foot skin reactions

7. Receiving long-term topical or systemic steroid treatment (except as part of pre-or post-medications of chemotherapy regime)

8. Pregnant or lactating mother

9. Participating in another interventional trial

10. Refuses to interrupt his/her usual care

11. Anticipated inability to follow-up

Related Conditions & MeSH terms

• Hand-Foot Syndrome
• Palmar-Plantar Erythrodysesthesia

Intervention

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

Locations

Country	Name	City	State
Malaysia	Sarawak General Hospital	Kuching	Sarawak

Sponsors (3)

Lead Sponsor	Collaborator
Sarawak General Hospital	Avantsar Sdn. Bhd., Universiti Sains Malaysia

Country where clinical trial is conducted

Malaysia, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Overall adverse events	Frequency of overall adverse events	At Day 22, Day 43, Day 64, and Day 127 of cream treatment
Secondary	Dermatology-related adverse events	Frequency of dermatology-related adverse events	At Day 22, Day 43, Day 64, and Day 127 of cream treatment