Aprepitant in the Prevention of Cisplatin-induced Delayed Emesis

Phase 3

Terminated

• Conditions: Emesis
• Interventions: Drug: aprepitant + dexamethasone; Drug: metoclopramide + dexamethasone

• Registration Number: NCT00869310
• Lead Sponsor: S. Maria Hospital, Terni

Brief Summary

The aim of the study is to compare efficacy and tolerability of aprepitant plus dexamethasone versus metoclopramide plus dexamethasone in the prevention of cisplatin-induced delayed emesis in patients that received aprepitant, palonosetron and dexamethasone before chemotherapy administration for the prevention of acute emesis.

Detailed Description

This is a phase III, double-blind, randomized trial, to evaluated the efficacy and safety of aprepitant for the prevention of delayed emesis in patients submitted for the first time to chemotherapy with cisplatin.

The study will be carried out during the first cycle of chemotherapy.

For the prevention of acute emesis, all patients will receive, before chemotherapy:

* dexamethasone 12 mg iv, in 15 minutes, 30 minutes before chemotherapy

* palonosetron 0.25 mg iv bolus, 30 minutes before chemotherapy

* aprepitant 125 mg orally, 60 minutes before chemotherapy

After 24 hours from chemotherapy administration, patients will be randomized to receive one of the following antiemetic treatments:

A) dexamethasone 8 mg orally: 24 hours after chemotherapy and at 8 pm on day 2, then at 8 am and 8 pm on days 3-4 plus Metoclopramide 20 mg orally 4 times a day: 24 hours after chemotherapy and then at 4 pm, 7 pm, 10 pm on day 2 then at 7 am, 12 am, 5 pm, 10 pm on days 3-4.

B) Dexamethasone 8 mg orally: 24 hours after chemotherapy (day 2) and then at 8 am on days 3-4 plus Aprepitant 80 mg orally: 24 hours after chemotherapy on day 2 and then at 8 am on day 3.

The patients will receive prochlorperazine suppositories as rescue medication, for important nausea and vomiting (\> 2 episodes) during days 1-5 after chemotherapy.

The patients will receive a diary, which includes a Visual Analogue Scale (VAS) for nausea and vomiting evaluation. All patients will fill out the diary, in which, for 6 consecutive days (days 1-6), patients will report for each day the number of vomiting episodes, the intensity and duration of nausea, any antiemetic rescue medication and any adverse event and its treatment.

In addition, on day 1 before chemotherapy and then on day 6, patients have to fill out the FLIE (Functional Living Index-Emesis), a questionnaire concerning the impact of nausea and vomiting on their quality of life.

Primary end-point is the percentage of complete responses (no vomiting and no rescue treatment) on days 2-5 after cisplatin administration

Study Timeline

• Study First Submitted: 2009-03-24
• Study First Submitted QC: 2009-03-24
• Study First Posted: 2009-03-25
• Study Start: 2009-09
• Primary Completion: 2012-05
• Study Completion: 2012-05
• Status Verified: 2014-01
• Last Update Submitted: 2014-01-03
• Last Update Posted: 2014-01-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 303

Inclusion Criteria

1. patients receiving for the first time chemotherapy with cisplatin at doses ≥50 mg/m2.
2. patients over 18 years old and those who signed informed consent
3. adequate contraception if premenopausal women.

Every other anticancer drug in the first 24 hours will be administered after the end of cisplatin.

Exclusion Criteria

1. patients receiving other anticancer drugs on days 2-4, except 5-fluorouracil, VP16, VM26, vincristine, vinblastine, vindesine, vinorelbine, gemcitabine
2. patients already submitted to chemotherapy with cisplatin
3. patients with concomitant severe diseases, other than neoplasm, or with predisposition to emesis such as intestinal obstruction, active peptic ulcer, hypercalcemia and brain metastases
4. contraindications to corticosteroids (i.e., active peptic ulcer or previous bleeding from peptic ulcer
5. patients submitted to concomitant radiotherapy or submitted to radiotherapy in the 15 days before chemotherapy or planned to receive radiotherapy during the 8 days after chemotherapy
6. patients receiving other concomitant antiemetic treatments or submitted to antiemetic treatments in the 24 hours before chemotherapy
7. patients with nausea or vomiting in the 24 hours before chemotherapy
8. patients receiving concomitant steroids, except when administered at physiologic dose
9. patients receiving concomitant benzodiazepines, except when used for nocturnal sedation
10. patients with WBC count <3000/mm3 or platelet count <70000/mm3
11. patients who are pregnant

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	aprepitant + dexamethasone	Dexamethasone plus Aprepitant
2	metoclopramide + dexamethasone	dexamethasone plus metoclopramide

Primary Outcome Measures

Name	Time	Method
Percentage of complete responses (no vomiting and no rescue treatment) on days 2-5 after cisplatin administration	6 days

Secondary Outcome Measures

Name	Time	Method
Evaluation of the impact on quality of life of the two antiemetic regimens	6 days
Evaluation of the prognostic factors of delayed emesis in patients receiving a combination of aprepitant, palonosetron, dexamethasone for the prevention of acute emesis	6 days

Trial Locations

Locations (1)

Fausto Roila; 🇮🇹 Terni, Italy