Aprepitant in the Prevention of Delayed Emesis Induced by Cyclophosphamide Plus Anthracyclines in Breast Cancer Patients - Full Text View

Sponsored by:	S. Maria Hospital, Terni
Information provided by:	S. Maria Hospital, Terni
ClinicalTrials.gov Identifier:	NCT00869973

Purpose

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	Intervention	Phase
Emesis	Drug: Aprepitant Drug: dexamethasone	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Nausea and Vomiting

Drug Information available for: Dexamethasone Cyclophosphamide Dexamethasone acetate Doxiproct plus Aprepitant Dexamethasone Sodium Phosphate

U.S. FDA Resources

Further study details as provided by S. Maria Hospital, Terni:

Primary Outcome Measures:

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

Secondary Outcome Measures:

Evaluation of the impact on quality of life of the two antiemetic regimens [ Time Frame: 6 days ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	800
Study Start Date:	April 2009
Estimated Study Completion Date:	May 2010
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Aprepitant	Drug: Aprepitant Aprepitant 80 mg orally: 24 hours after chemotherapy on day 2 and then at 8 am on day 3
2: Active Comparator 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

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00869973

Contacts

Contact: Fausto Roila, MD

+39(0)744205631

roila.fausto@libero.it

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:

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.

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.

[No authors listed] 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.

Responsible Party:	Oncology Division, S.Maria Hospital, Terni, Italy ( Roila Fausto )
Study ID Numbers:	IGAR-02-2009, 2008-001237-95
Study First Received:	March 25, 2009
Last Updated:	March 25, 2009
ClinicalTrials.gov Identifier:	NCT00869973 History of Changes
Health Authority:	Italy: Ministry of Health

Keywords provided by S. Maria Hospital, Terni:

aprepitant
delayed emesis
cyclophosphamide plus anthracyclines
breast cancer
antiemetic

Study placed in the following topic categories:

Anti-Inflammatory Agents
Dexamethasone
Vomiting
Antineoplastic Agents, Hormonal
Skin Diseases
Signs and Symptoms, Digestive
Immunologic Factors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Breast Neoplasms
Antiemetics
Cyclophosphamide

Hormones
Glucocorticoids
Immunosuppressive Agents
Signs and Symptoms
Peripheral Nervous System Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents
Breast Diseases
Dexamethasone acetate
Aprepitant

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Dexamethasone
Vomiting
Signs and Symptoms, Digestive
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Cyclophosphamide
Hormones
Signs and Symptoms
Neoplasms by Site
Therapeutic Uses

Alkylating Agents
Dexamethasone acetate
Breast Diseases
Aprepitant
Antineoplastic Agents, Hormonal
Skin Diseases
Gastrointestinal Agents
Breast Neoplasms
Glucocorticoids
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Autonomic Agents
Myeloablative Agonists
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on September 09, 2009