Safety and Efficacy of Aprepitant for CINV in Patients With Lung Cancer Receiving Multiple-day Cisplatin Chemotherapy

Phase 2

• Conditions: Chemotherapy-Induced Nausea and Vomiting; Lung Cancer
• Interventions: Drug: Aprepitant; Drug: Palonosetron; Drug: Dexamethasone

• Registration Number: NCT02445872
• Lead Sponsor: Zhejiang University

Brief Summary

Aprepitant is an oral neurokinin-1(NK-1) antagonist which is used for the prevention of chemotherapy-induced nausea and vomiting (CINV). This phase II clinical trial was designed to evaluate the efficacy of aprepitant in the prevention of CINV with lung cancer patients receiving 3-day cisplatin-based chemotherapy.

Detailed Description

Patients pathologic diagnosed of advanced non-small cell lung cancer, according to NCCN non-small cell lung cancer guide line(2015 V1).The patient should receive a 3-day cisplatin-based chemotherapy, are randomized divided into two groups, aprepitant group and placebo group. In aprepitant group, patients would receive aprepitant(125 mg po at day1, 80 mg at day2-3) combination with palonosetron and dexamethasone(5mg iv at day1-3, 3.75mg po at day4-5). In placebo group patients would receive palonosetron and dexamethasone(5mg iv at day1-3, 7.5mg po at day4-5).During the treatment, any grade of nausea and vomiting should be recorded in order to evaluate the complete response rate of CINV, other side-effects should be recorded.

Study Timeline

• Study First Submitted: 2015-04-05
• Study First Submitted QC: 2015-05-14
• Study First Posted: 2015-05-15
• Status Verified: 2015-08
• Study Start: 2015-12
• Last Update Submitted: 2015-12-08
• Last Update Posted: 2015-12-09
• Primary Completion: 2016-05
• Study Completion: 2016-05

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Patient who was confirmed lung cancer by pathologic histology or cytology.
2. Males or females aged ≥18 years, <80 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Life expectancy ≥12 weeks.
4. Males and females should be contraceptive during the period of the trial until 8 weeks after the last administration of the drug.
5. Patients with asymptomatic, treated brain metastases are eligible for trial participation.
6. Adequate bone marrow, renal, and liver function are required.
7. Able to comply with the required protocol and follow-up procedures, and able to receive oral medications.
8. Institutional review board-approved informed consent will be obtained for every patient before initiation of any trial-specific procedure or treatment.

Exclusion Criteria

1. History of sensitivity/idiosyncrasy to aprepitant or excipients
2. Condition that might interfere with drug absorption, distribution metabolism or excretion.
3. Concomitant use of agents that are known to interfere with aprepitant pharmacokinetics
4. Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).
5. Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome, or inability to take oral medication, or have active peptic ulcer disease.
6. Female subjects should not be pregnant or breast-feeding.
7. Inadequate hematological function.
8. Abnormal liver and renal function.
9. Patient assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	Palonosetron	Aprepitant: 125mg PO on day1, 80mg PO on day2 and day3. Palonosetron (a 5-HT3 receptor antagonist): 0.25 mg IV push on day 1 only. Dexamethasone: 5mg IV push once daily from day 1 to day 3,and 3.75mg PO on days 4-5.
Arm A	Dexamethasone	Aprepitant: 125mg PO on day1, 80mg PO on day2 and day3. Palonosetron (a 5-HT3 receptor antagonist): 0.25 mg IV push on day 1 only. Dexamethasone: 5mg IV push once daily from day 1 to day 3,and 3.75mg PO on days 4-5.
Arm A	Aprepitant	Aprepitant: 125mg PO on day1, 80mg PO on day2 and day3. Palonosetron (a 5-HT3 receptor antagonist): 0.25 mg IV push on day 1 only. Dexamethasone: 5mg IV push once daily from day 1 to day 3,and 3.75mg PO on days 4-5.
Arm B	Palonosetron	Palonosetron: 0.25 mg IV push on day 1 only. Dexamethasone: 5mg IV push once daily from day 1 to day 3,and 7.5mg PO on days 4-5.
Arm B	Dexamethasone	Palonosetron: 0.25 mg IV push on day 1 only. Dexamethasone: 5mg IV push once daily from day 1 to day 3,and 7.5mg PO on days 4-5.

Primary Outcome Measures

Name	Time	Method
Complete Response	5 days after the end of chemotherapy	The primary endpoint is the overall rate of patients achieving a complete response (defined as no emetic episode and no use of rescue medication) during the overall phase

Secondary Outcome Measures

Name	Time	Method
Presence of nausea	5 days after the end of chemotherapy	Presence of nausea graded according to Likert scale (none, mild, moderate and severe)
Complete Control (No emetic episode, no need for rescue medication, with a maximum grade of mild nausea)	5 days after the end of chemotherapy	No emetic episode, no need for rescue medication, with a maximum grade of mild nausea
Emesis-free	5 days after the end of chemotherapy	Percentage of patients without emetic episodes
Safety and tolerability (adverse events related to study drug administration)	5 days after the end of chemotherapy	Number of patients experienced at least one adverse events related to study drug administration.

Trial Locations

Locations (1)

The first affiliated hospital, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China