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

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ClinicalTrials.gov Identifier: NCT00869973

Recruitment Status : Terminated (We terminated the study after enrolling 580/900 patients due to a slow accrual)

First Posted : March 26, 2009

Last Update Posted : January 23, 2013

Sponsor:

Information provided by (Responsible Party):

Roila Fausto, S. Maria Hospital, Terni

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Emesis	Drug: Aprepitant Drug: dexamethasone	Phase 3

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 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

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	580 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
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
Study Start Date :	September 2009
Actual Primary Completion Date :	July 2012
Actual Study Completion Date :	July 2012

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Breast cancer

MedlinePlus related topics: Breast Cancer Nausea and Vomiting

Drug Information available for: Dexamethasone Cyclophosphamide Aprepitant

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 Aprepitant	Drug: Aprepitant Aprepitant 80 mg orally: 24 hours after chemotherapy on day 2 and then at 8 am on day 3
Active Comparator: 2 dexamethasone	Drug: 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

Outcome Measures

Primary Outcome Measures :

Percentage of complete responses (no vomiting and no rescue treatment) on days 2-5 after chemotherapy administration [ Time Frame: 6 days ]

Secondary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00869973

Locations


Italy
Fausto Roila
Terni, Italy, 05100

Sponsors and Collaborators

S. Maria Hospital, Terni

Investigators


Principal Investigator:	Fausto Roila, MD	Oncology Division, S. Maria Hospital, Terni, Italy

More Information

Publications of Results:

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-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol. 2005 Apr 20;23(12):2822-30. Erratum in: J Clin Oncol. 2005 Aug 20;23(24):5851. Dosage error in published abstract; MEDLINE/PubMed abstract corrected.

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. Ann Oncol. 2006 Jan;17(1):20-8. Epub 2005 Nov 28.

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 pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Cancer. 2003 Dec 1;98(11):2473-82.

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 double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol. 2003 Oct;14(10):1570-7.

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. 2004 May 15;22(10):2038.

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Roila F, Ruggeri B, Ballatori E, Del Favero A, Tonato M. Aprepitant versus dexamethasone for preventing chemotherapy-induced delayed emesis in patients with breast cancer: a randomized double-blind study. J Clin Oncol. 2014 Jan 10;32(2):101-6. doi: 10.1200/JCO.2013.51.4547. Epub 2013 Dec 9.


Responsible Party:	Roila Fausto, Dr, S. Maria Hospital, Terni
ClinicalTrials.gov Identifier:	NCT00869973 History of Changes
Other Study ID Numbers:	IGAR-02-2009 2008-001237-95
First Posted:	March 26, 2009 Key Record Dates
Last Update Posted:	January 23, 2013
Last Verified:	October 2009

Keywords provided by Roila Fausto, S. Maria Hospital, Terni:


aprepitant delayed emesis cyclophosphamide plus anthracyclines breast cancer antiemetic

Additional relevant MeSH terms:


Breast Neoplasms Vomiting Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Signs and Symptoms, Digestive Signs and Symptoms Dexamethasone acetate Dexamethasone Aprepitant Fosaprepitant Cyclophosphamide BB 1101 Anti-Inflammatory Agents	Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors

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