Aprepitant vs. Desloratadine in EGFR-TKIs Related Pruritus Treatment

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Aprepitant
* Drug: Desloratadine
* Drug: Placebo of aprepitant
* Drug: Placebo of desloratadine


Participation Criteria
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Eligibility Criteria
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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.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aprepitant and placebo<br>aprepitant 125mg d1, 80mg d3 and d5, along with placebo 5mg d1-d28; | Drug: Aprepitant<br>* aprepitant 125mg d1, 80mg d3 and d5; until pruritus recurrence or discontinuation of EGFR-TKI or safely issues (SAE etc.)<br>* Other names: Treatment arm: Aprepitant administration;Drug: Placebo of desloratadine<br>* Placebo of desloratadine 5mg d1-d28; until pruritus recurrence or discontinuation of EGFR-TKI or safely issues (SAE etc.)<br>* Other names: Comparative arm: Placebo of Desloratadine administration;|
| Active Comparator: desloratadine and placebo<br>placebo 125mg d1, 80mg d3 and d5, along with desloratadine 5mg d1-d28 | Drug: Desloratadine<br>* Desloratadine 5mg d1-d28; until pruritus recurrence or discontinuation of EGFR-TKI or safely issues (SAE etc.)<br>* Other names: Treatment arm: Desloratadine administration;Drug: Placebo of aprepitant<br>* Placebo of aprepitant 125mg d1, 80mg d3 and d5; until pruritus recurrence or discontinuation of EGFR-TKI or safely issues (SAE etc.)<br>* Other names: Comparative arm: Placebo of aprepitant administration;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pruritus, Non-small Cell Lung Cancer, Receptor, Epidermal Growth Factor, tyrosine kinase inhibitor