Aprepitant vs. Desloratadine in EGFR-TKIs Related Pruritus Treatment

Non-small Cell Lung Cancer Clinical Trial

— EGFR-TKIs  

Official title:

Aprepitant vs. Desloratadine in Non-small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Related Pruritus: A Prospective, Randomized Control, Double-blinded, Phase II Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02646020
• Other study ID #: TAPE001
• Status: Completed
• Phase: Phase 2
• Start date: December 2015
• Est. completion date: December 1, 2020

Study information

• Verified date: May 2021
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study hypothesis is that aprepitant is more effective than desloratadine in relieving pruritus caused by EGFR TKIs. Primary endpoint is the effective rate of pruritus, effective treatment defined as visual analogue scale (VAS) decrease ≥ 50% after treatment compared to baseline score. 130 NSCLC patients undertaken EGFR-TKI and suffer from moderate or severe pruritus (VAS score ≥ 4) will be enrolled in this study, and stratified (gender, VAS 4-6 or 7-10, and 2nd generation TKI or non 2nd generation) randomized (1:1) into aprepitant or desloratadine treatment. VAS investigation will be taken once a week to treatment end (4 weeks).

Description:

This is a prospective, randomized control, double-blinded, phase II clinical trial. Study hypothesis is that aprepitant is more effective than desloratadine in relieving pruritus caused by EGFR TKIs. Primary endpoint is the effective rate of pruritus, effective treatment defined as visual analogue scale (VAS) decrease ≥ 50% after treatment (1 week) compared to baseline score. The VAS inquiry will be taken once a week for 4 weeks. Quality of life investigation will be performed at baseline, 1 week and 4 weeks after treatment using SKINDEX-16 questionnaire. 130 NSCLC patients undertaken EGFR-TKI and suffer from moderate or severe pruritus (VAS score ≥ 4) will be enrolled in this study, and stratified (gender,and VAS 4-6 or 7-10, and 2nd generation TKI or non 2nd generation) randomized (1:1) into aprepitant or desloratadine treatment. Aprepitant arm will be administrated aprepitant 125mg d1, 80mg d3 and d5, along with placebo 5mg d1-d28; desloratadine arm will be administrated placebo 125mg d1, 80mg d3 and d5, along with desloratadine 5mg d1-d28. Tolerance evaluation will be taken according to National Cancer Institute (NCI)-Common Terminology Criteria (CTC) For Adverse Events (AE) V4.03.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 138
• Est. completion date: December 1, 2020
• Est. primary completion date: October 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Advanced or metastatic non small cell lung cancer
• Undertaken EGFR TKIs treatment (gefitinib, erlotinib, icotinib, afatinib, etc)
• 18 years old
• Eastern Cooperative Oncology Group (ECOG) performance score 0-2
• Moderate or severe pruritus (VAS score = 4) first occur after EGFR TKIs treatment
• Life expectancy = 3 months
• Orally drug administration with no difficulty
• pregnancy test negative in 7 days for women of child-bearing age; willing to take contraception measures.
• Signed informed consent form (ICF)

Exclusion Criteria:

• Systemically treatment with Neurokinin-1 (NK-1) receptor inhibitors, antihistamines drugs, antibiotics, cortical hormone therapy, antiepileptic drugs, immunosuppressive agents or other drugs might affect treatment in 4 weeks; or locally used of these drug in 2 weeks.
• Existing skin lesions not EGFR TKIs related, such as skin infection, chronic dermatitis, Systemic Lupus Erythematosus (SLE), lymphoma or other diseases.
• Total bilirubin = 1.5 Upper Limit Of Normal (ULN)
• Serum creatinine =mg/dl
• AST or ALT = 2.5 ULN without liver metastasis; or = 5 ULN with liver metastasis.
• Residual toxicity event = CTC-AE grade 2, except peripheral neurotoxicities.
• Central nervous system (CNS) metastasis or spinal compression; except no symptoms and with no cortical hormonotherapy in 4 weeks.
• Clinical evidence of interstitial lung disease
• Any severe or uncontrolled systemic diseases judged by investigators.
• Any contraindication of Neurokinin-1 receptor inhibitors and desloratadine. Discontinuation Criteria
• Invalid subject after randomization
• Major protocol violations judged by investigators.
• Poor compliance
• Intolerable adverse events
• Subject withdraw ICF
• Any pregnancy events
• No clinical benefits due to clinical adverse events, laboratory abnormalities or other medical conditions
• Other reasons of treatment discontinuation judged by investigators.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer
• Pruritus

Intervention

Drug:
• Aprepitant
aprepitant 125mg d1, 80mg d3 and d5; until pruritus recurrence or discontinuation of EGFR-TKI or safely issues (SAE etc.)
• Desloratadine
Desloratadine 5mg d1-d28; until pruritus recurrence or discontinuation of EGFR-TKI or safely issues (SAE etc.)
• Placebo of aprepitant
Placebo of aprepitant 125mg d1, 80mg d3 and d5; until pruritus recurrence or discontinuation of EGFR-TKI or safely issues (SAE etc.)
• Placebo of desloratadine
Placebo of desloratadine 5mg d1-d28; until pruritus recurrence or discontinuation of EGFR-TKI or safely issues (SAE etc.)

Locations

Country	Name	City	State
China	Cancer Center of Sun-Yat Sen University (CCSYSU)	GuangZhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (23)

Bachert C, Maurer M. Safety and efficacy of desloratadine in subjects with seasonal allergic rhinitis or chronic urticaria: results of four postmarketing surveillance studies. Clin Drug Investig. 2010;30(2):109-22. doi: 10.2165/11530930-000000000-00000. R — View Citation

Booken N, Heck M, Nicolay JP, Klemke CD, Goerdt S, Utikal J. Oral aprepitant in the therapy of refractory pruritus in erythrodermic cutaneous T-cell lymphoma. Br J Dermatol. 2011 Mar;164(3):665-7. doi: 10.1111/j.1365-2133.2010.10108.x. Epub 2011 Jan 28. — View Citation

Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczésna A, Juhász E, Esteban E, Molinier O, Brugger W, Melezínek I, Klingelschmitt G, Klughammer B, Giaccone G; SATURN investigators. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer — View Citation

Chan A, Tan EH. How well does the MESTT correlate with CTCAE scale for the grading of dermatological toxicities associated with oral tyrosine kinase inhibitors? Support Care Cancer. 2011 Oct;19(10):1667-74. doi: 10.1007/s00520-010-0999-2. Epub 2010 Sep 5. — View Citation

Chang SE, Han SS, Jung HJ, Choi JH. Neuropeptides and their receptors in psoriatic skin in relation to pruritus. Br J Dermatol. 2007 Jun;156(6):1272-7. — View Citation

Grob JJ, Auquier P, Dreyfus I, Ortonne JP. Quality of life in adults with chronic idiopathic urticaria receiving desloratadine: a randomized, double-blind, multicentre, placebo-controlled study. J Eur Acad Dermatol Venereol. 2008 Jan;22(1):87-93. doi: 10. — View Citation

Jiménez Gallo D, Albarrán Planelles C, Linares Barrios M, Fernández Anguita MJ, Márquez Enríquez J, Rodríguez Mateos ME. Treatment of pruritus in early-stage hypopigmented mycosis fungoides with aprepitant. Dermatol Ther. 2014 May-Jun;27(3):178-82. doi: 1 — View Citation

Lacouture ME, Anadkat MJ, Bensadoun RJ, Bryce J, Chan A, Epstein JB, Eaby-Sandy B, Murphy BA; MASCC Skin Toxicity Study Group. Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care — View Citation

Lynch TJ Jr, Kim ES, Eaby B, Garey J, West DP, Lacouture ME. Epidermal growth factor receptor inhibitor-associated cutaneous toxicities: an evolving paradigm in clinical management. Oncologist. 2007 May;12(5):610-21. Review. — View Citation

Marquez D, Ramonda C, Lauxmann JE, Romero CA, Vukelic VL, Martinatto C, Barrón B, Novoa PA, Peixoto AJ, Orías M. Uremic pruritus in hemodialysis patients: treatment with desloratidine versus gabapentin. J Bras Nefrol. 2012 Jun;34(2):148-52. — View Citation

Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary — View Citation

Ocvirk J, Cencelj S. Management of cutaneous side-effects of cetuximab therapy in patients with metastatic colorectal cancer. J Eur Acad Dermatol Venereol. 2010 Apr;24(4):453-9. doi: 10.1111/j.1468-3083.2009.03446.x. Epub 2009 Sep 27. — View Citation

Ortonne JP, Grob JJ, Auquier P, Dreyfus I. Efficacy and safety of desloratadine in adults with chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, multicenter trial. Am J Clin Dermatol. 2007;8(1):37-42. — View Citation

Porzio G, Aielli F, Verna L, Porto C, Tudini M, Cannita K, Ficorella C. Efficacy of pregabalin in the management of cetuximab-related itch. J Pain Symptom Manage. 2006 Nov;32(5):397-8. — View Citation

Quartara L, Altamura M. Tachykinin receptors antagonists: from research to clinic. Curr Drug Targets. 2006 Aug;7(8):975-92. Review. — View Citation

Santini D, Vincenzi B, Guida FM, Imperatori M, Schiavon G, Venditti O, Frezza AM, Berti P, Tonini G. Aprepitant for management of severe pruritus related to biological cancer treatments: a pilot study. Lancet Oncol. 2012 Oct;13(10):1020-4. doi: 10.1016/S1 — View Citation

Scope A, Agero AL, Dusza SW, Myskowski PL, Lieb JA, Saltz L, Kemeny NE, Halpern AC. Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. J Clin Oncol. 2007 Dec 1;25(34):5390-6. — View Citation

Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L; National Cancer Institute of — View Citation

Ständer S, Siepmann D, Herrgott I, Sunderkötter C, Luger TA. Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy. PLoS One. 2010 Jun 4;5(6):e10968. doi: 10.1371/journal.pone.0010968. — View Citation

Ständer S, Weisshaar E. Medical treatment of pruritus. Expert Opin Emerg Drugs. 2012 Sep;17(3):335-45. doi: 10.1517/14728214.2012.711316. Epub 2012 Aug 7. Review. — View Citation

Vincenzi B, Fratto ME, Santini D, Tonini G. Aprepitant against pruritus in patients with solid tumours. Support Care Cancer. 2010 Sep;18(9):1229-30. doi: 10.1007/s00520-010-0895-9. Epub 2010 Jun 11. — View Citation

Zhang L, Ma S, Song X, Han B, Cheng Y, Huang C, Yang S, Liu X, Liu Y, Lu S, Wang J, Zhang S, Zhou C, Zhang X, Hayashi N, Wang M; INFORM investigators. Gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-smal — View Citation

Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Erlotinib versus chemotherapy as first-line treatment for patients with ad — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	effective rate of pruritus relieving	effective treatment of pruritus relieving defined as visual analogue scale (VAS) decrease = 50% after treatment compared to baseline score	day 28 at the treatment ends
Secondary	duration of pruritus relieving	the time from pruritus effective relief to VAS score increase = baseline level, the VAS inquiry will be taken once a week.	12 weeks at the follow-up end
Secondary	Change from baseline quality of life assessment at treatment ends	using SKINDEX-16 questionnaire to assess patients quality of life	baseline, 28 days at the treatment ends