Aprepitant in the Prevention of Delayed Emesis Induced by Cyclophosphamide Plus Anthracyclines in Breast Cancer Patients

Emesis Clinical Trial

Official title:

Aprepitant in the Prevention of Delayed Emesis Induced by Moderately Emetogenic Chemotherapy (Cyclophosphamide Plus Anthracyclines) in Breast Cancer Patients: a Double-blind Randomized Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00869973
• Other study ID #: IGAR-02-2009
• Secondary ID: 2008-001237-95
• Status: Terminated
• Phase: Phase 3
• First received: March 25, 2009
• Last updated: January 22, 2013
• Start date: September 2009
• Est. completion date: July 2012

Study information

• Verified date: October 2009
• Source: S. Maria Hospital, Terni
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to compare efficacy and tolerability of aprepitant versus dexamethasone in the prevention of delayed emesis induced by moderately emetogenic chemotherapy (cyclophosphamide plus anthracyclines) in breast cancer patients.

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 with breast cancer submitted for the first time to chemotherapy with cyclophosphamide plus anthracyclines.

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 8 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:

A) dexamethasone 4 mg orally: 24 hours after chemotherapy and at 8 pm on day 2, then at 8 am and 8 pm on day 3.

B) 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 will 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 chemotherapy administration

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 580
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• patients with breast cancer, receiving for the first time chemotherapy with cyclophosphamide + anthracyclines (FAC, FEC, AC, EC).

• patients over 18 years old and those who signed informed consent

• adequate contraception if premenopausal women

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

Exclusion Criteria:

• patients already submitted to chemotherapy

• patients receiving any chemotherapy on days 2-4 after treatment

• patients with concomitant severe diseases or with predisposition to emesis such as intestinal obstruction, active peptic ulcer, hypercalcemia and brain metastases

• contraindications to corticosteroids (i.e., active peptic ulcer or previous bleeding from peptic ulcer

• 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

• patients receiving other concomitant antiemetic treatments or submitted to antiemetic treatments in the 24 hours before chemotherapy

• patients with nausea or vomiting in the 24 hours before chemotherapy

• patients receiving concomitant steroids, except when administered at physiologic doses

• patients receiving concomitant benzodiazepines, except when used for nocturnal sedation

• patients with WBC count <3000/mm3 or platelet count <70000/mm3

• patients who are pregnant or breast-feeding

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Emesis
• Vomiting

Intervention

Drug:
• Aprepitant
Aprepitant 80 mg orally: 24 hours after chemotherapy on day 2 and then at 8 am on day 3
• dexamethasone
dexamethasone 4 mg orally: 24 hours after chemotherapy and at 8 pm on day 2, then at 8 am and 8 pm on day 3

Locations

Country	Name	City	State
Italy	Fausto Roila	Terni

Sponsors (1)

Lead Sponsor	Collaborator
S. Maria Hospital, Terni

Country where clinical trial is conducted

Italy, 

References & Publications (6)

Dexamethasone alone or in combination with ondansetron for the prevention of delayed nausea and vomiting induced by chemotherapy. The Italian Group for Antiemetic Research. N Engl J Med. 2000 May 25;342(21):1554-9. — View Citation

Eisenberg P, Figueroa-Vadillo J, Zamora R, Charu V, Hajdenberg J, Cartmell A, Macciocchi A, Grunberg S; 99-04 Palonosetron Study Group. Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologi — View Citation

Gralla R, Lichinitser M, Van Der Vegt S, Sleeboom H, Mezger J, Peschel C, Tonini G, Labianca R, Macciocchi A, Aapro M. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a — View Citation

Italian Group For Antiemetic Research. Randomized, double-blind, dose-finding study of dexamethasone in preventing acute emesis induced by anthracyclines, carboplatin, or cyclophosphamide:. J Clin Oncol. 2004 Feb 15;22(4):725-9. Erratum in: J Clin Oncol. — View Citation

Roila F, Hesketh PJ, Herrstedt J; Antiemetic Subcommitte of the Multinational Association of Supportive Care in Cancer. Prevention of chemotherapy- and radiotherapy-induced emesis: results of the 2004 Perugia International Antiemetic Consensus Conference. — View Citation

Warr DG, Hesketh PJ, Gralla RJ, Muss HB, Herrstedt J, Eisenberg PD, Raftopoulos H, Grunberg SM, Gabriel M, Rodgers A, Bohidar N, Klinger G, Hustad CM, Horgan KJ, Skobieranda F. Efficacy and tolerability of aprepitant for the prevention of chemotherapy-ind — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of complete responses (no vomiting and no rescue treatment) on days 2-5 after chemotherapy administration		6 days	Yes
Secondary	Evaluation of the impact on quality of life of the two antiemetic regimens		6 days	Yes
Secondary	Evaluation of the prognostic factors of delayed emesis in patients receiving a combination of aprepitant, palonosetron and dexamethasone for the prevention of acute emesis		6 days	Yes