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

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

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.

Study Overview

• Status: Unknown
• Conditions: Lung Cancer; Chemotherapy-Induced Nausea and Vomiting
• Intervention / Treatment: Drug: Dexamethasone; Drug: Palonosetron; Drug: Aprepitant

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 Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Qiong Zhao, MD; Phone Number: 0571-87236802; Email: doczq.2008@gmail.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; 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.	Drug: Dexamethasone; Drug: Palonosetron; Drug: Aprepitant; Aprepitant:The first day, one 125 mg capsule will be administered per oral, 1 hour before chemotherapy. Thereafter one 80 mg capsule will be repeated daily between 8 to 10 a.m. during days 2 to 3; Other Names: Emend
Active Comparator: Arm B; 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.	Drug: Dexamethasone; Drug: Palonosetron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response	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	5 days after the end of chemotherapy

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Qiong Zhao, MD, The First Affiliated Hospital, Zhejiang University

Publications and helpful links

General Publications

• Gao HF, Liang Y, Zhou NN, Zhang DS, Wu HY. Aprepitant plus palonosetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving multiple-day cisplatin chemotherapy. Intern Med J. 2013 Jan;43(1):73-6. doi: 10.1111/j.1445-5994.2011.02637.x.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Anticipated): May 1, 2016
• Study Completion (Anticipated): May 1, 2016

Study Registration Dates

• First Submitted: April 5, 2015
• First Submitted That Met QC Criteria: May 14, 2015
• First Posted (Estimate): May 15, 2015

Study Record Updates

• Last Update Posted (Estimate): December 9, 2015
• Last Update Submitted That Met QC Criteria: December 8, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Chemotherapy-induced Nausea and Vomiting; Nausea; Vomiting; Lung cancer; Aprepitant; CINV
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Signs and Symptoms, Digestive; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Neurokinin-1 Receptor Antagonists; Dexamethasone; Palonosetron; Aprepitant
• Other Study ID Numbers: ZYTOP1502