Official Title: “Efficacy of Palonosetron in the Prevention of Acute and Delayed Chemotherapy-Induced Nausea and Vomiting Following Dose Dense Adriamycin-Cyclophosphamide Chemotherapy in Early Stage Breast Cancer Patients”

RATIONALE: Antiemetic drugs, such as dexamethasone, ondansetron, and palonosetron, may help lessen or prevent nausea and vomiting caused by chemotherapy.

PURPOSE: This clinical trial is studying how well giving dexamethasone together with ondansetron or palonosetron works in preventing nausea and vomiting in patients undergoing chemotherapy for early-stage breast cancer.

Study Type: Interventional

Study Design: Supportive Care, Open Label

Study Primary Completion Date: August 2010

OBJECTIVES:

Primary - Determine the complete response (CR) rate, defined as no emesis and no rescue medications in the 0-24 hour time period after weekly intravenous doxorubicin hydrochloride, in patients with early-stage breast cancer treated with dexamethasone in combination with either ondansetron or palonosetron.

Secondary - Determine the proportion of patients achieving CR, defined as no emesis and no rescue medications in the 24-120 hour time period after weekly intravenous doxorubicin hydrochloride. - Determine the proportion of patients achieving CR, defined as no emesis and no rescue medications in the 0-120 hour time period after weekly intravenous doxorubicin hydrochloride. - Determine the number of emetic episodes daily and cumulatively for the 24-120 and 0-120 hour time periods in these patients. - Determine the time to first emetic episode in these patients. - Determine the time to first administration of rescue medication in these patients. - Determine the time to treatment failure, defined as the time to first emetic episode or administration of rescue medication, whichever occurs first, in these patients. - Determine the number of doses of rescue medications used in these patients. - Determine the side effects of this regimen in these patients. - Determine the severity of nausea in these patients. - Determine the quality of life of these patients.

OUTLINE: This is a multicenter study. The first 7 patients enrolled in the study are assigned to group 1. After treatment in group 1 is completed, subsequent patients enrolled in the study are assigned to group 2.

All patients receive metronomic chemotherapy comprising doxorubicin hydrochloride IV on day 1 and oral cyclophosphamide on days 1-7. Treatment repeats every 7 days for 12-15 courses. - Group 1: Patients receive standard antiemetic therapy comprising dexamethasone IV and ondansetron IV prior to each dose of doxorubicin hydrochloride. - Group 2: Patients receive dexamethasone IV and palonosetron hydrochloride IV prior to each dose of doxorubicin hydrochloride.

Patients may receive rescue antiemetic medication after chemotherapy at the discretion of the investigator.

Quality of life is assessed at baseline and on day 5 of each course.

PROJECTED ACCRUAL: A total of 57 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: cyclophosphamide
• Drug: dexamethasone
• Drug: doxorubicin hydrochloride
• Drug: ondansetron
• Drug: palonosetron hydrochloride
• Procedure: quality-of-life assessment

DISEASE CHARACTERISTICS:

• Histologically confirmed primary breast carcinoma
• Early-stage disease
• Chemotherapy-naïve disease
• Must be planning to undergo chemotherapy comprising weekly intravenous doxorubicin hydrochloride and daily oral cyclophosphamide
• No vomiting, retching, or grade 2-4 nausea in the 24 hours preceding chemotherapy
• No ongoing vomiting from any organic etiology

PATIENT CHARACTERISTICS:

• Karnofsky performance status 50-100%
• Patients with known mild to moderate hepatic, renal, or cardiovascular impairment may be enrolled at the discretion of the investigator
• No known contraindication to 5-HT3 receptor antagonists (including palonosetron hydrochloride) or dexamethasone

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 30 days since prior investigational drugs
• No other drugs with potential antiemetic effect within 24 hours prior to starting chemotherapy, including any of the following:
• 5-HT3 receptor antagonists
• Dopamine-receptor antagonists (e.g., metoclopramide)
• Phenothiazine antiemetics (e.g., prochlorperazine, thiethylperazine, or perphenazine)
• Diphenhydramine
• Diphenhydramine allowed if given for prophylactic treatment of hypersensitivity reactions associated with the administration of taxanes
• Scopolamine
• Chlorpheniramine maleate
• Trimethobenzamide
• All benzodiazepines
• Haloperidol
• Droperidol
• Tetrahydrocannabinol
• Nabilone
• Any systemic corticosteroid (e.g., hydrocortisone, methylprednisolone, or prednisone)
• Topical or inhaled preparations allowed
• No other concurrent systemic corticosteroids except for the following:
• Corticosteroids given as part of the chemotherapy regimen as a preventative measure for chemotherapy toxicities
• Topical or inhaled preparations
• Corticosteroids used as rescue medication during the study
• No concurrent radiotherapy

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Fred Hutchinson Cancer Research Center

Overall Clinical Trial Officials and Contacts

Hannah M. Linden, MD Study Chair Seattle Cancer Care Alliance  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00343863

Study ID Number: CDR0000475746

ClinicalTrials.gov Identifier: NCT00343863

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database