Aprepitant vs. Desloratadine in EGFR-TKIs Related Pruritus Treatment

Sponsor

Sun Yat-sen University (Other)

Overall Status

Completed

CT.gov ID

NCT02646020

Collaborator

(none)

138

Enrollment

Location

Arms

Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: Aprepitant Drug: Desloratadine Drug: Placebo of aprepitant Drug: Placebo of desloratadine	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

138 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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

Study Start Date :

Dec 1, 2015

Actual Primary Completion Date :

Oct 1, 2020

Actual Study Completion Date :

Dec 1, 2020

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Aprepitant and placebo

aprepitant 125mg d1, 80mg d3 and d5, along with placebo 5mg d1-d28;

Drug: Aprepitant

aprepitant 125mg d1, 80mg d3 and d5; until pruritus recurrence or discontinuation of EGFR-TKI or safely issues (SAE etc.)

Other Names:

Treatment arm: Aprepitant administration

Drug: Placebo of desloratadine

Placebo of desloratadine 5mg d1-d28; until pruritus recurrence or discontinuation of EGFR-TKI or safely issues (SAE etc.)

Other Names:

Comparative arm: Placebo of Desloratadine administration

Active Comparator: desloratadine and placebo

placebo 125mg d1, 80mg d3 and d5, along with desloratadine 5mg d1-d28

Drug: Desloratadine

Desloratadine 5mg d1-d28; until pruritus recurrence or discontinuation of EGFR-TKI or safely issues (SAE etc.)

Other Names:

Treatment arm: Desloratadine administration

Drug: 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.)

Other Names:

Comparative arm: Placebo of aprepitant administration

Outcome Measures

Primary Outcome Measures

effective rate of pruritus relieving [day 28 at the treatment ends]
effective treatment of pruritus relieving defined as visual analogue scale (VAS) decrease ≥ 50% after treatment compared to baseline score

Secondary Outcome Measures

duration of pruritus relieving [12 weeks at the follow-up end]
the time from pruritus effective relief to VAS score increase ≥ baseline level, the VAS inquiry will be taken once a week.
Change from baseline quality of life assessment at treatment ends [baseline, 28 days at the treatment ends]
using SKINDEX-16 questionnaire to assess patients quality of life

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.