Dexamethasone and Ondansetron Hydrochloride or Palonosetron Hydrochloride in Preventing Nausea and Vomiting in Patients Receiving Doxorubicin Hydrochloride and Cyclophosphamide For Early Stage Breast Cancer

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 hydrochloride, and palonosetron hydrochloride, may help lessen or prevent nausea and vomiting caused by chemotherapy.

PURPOSE: This clinical trial studies how well giving dexamethasone together with ondansetron hydrochloride or palonosetron hydrochloride works in preventing nausea and vomiting in patients receiving doxorubicin hydrochloride and cyclophosphamide for early stage breast cancer

PRIMARY OBJECTIVES:

I. To determine the proportion of patients achieving a complete response (CR), defined as no emesis and no rescue medications in the 0-24 hour time period following weekly intravenous doxorubicin.

SECONDARY OBJECTIVES:

I. To determine the proportion of patients achieving a complete response (CR), defined as no emesis and no rescue medications in the 24-120 hour time period following weekly intravenous doxorubicin.

II. To determine the proportion of patients achieving a complete response (CR), defined as no emesis and no rescue medications in the 0-120 hour time period following weekly intravenous doxorubicin.

III. To determine the number of emetic episodes daily and cumulatively for the 24-120, and 0-120 hour time periods.

IV. To determine the time to first emetic episode. V. To determine the time to first administration of rescue medication. VI. To determine the time to treatment failure (time to first emetic episode or administration of rescue medication, whichever occurred first).

VII. To determine the number of doses of rescue medications used. VIII. To determine the side effects of antiemetic medications used. IX. To determine theseverity of nausea. X. To evaluate quality of life.

OUTLINE: Patients are assigned to 1 of 2 treatment groups.

All patients receive doxorubicin hydrochloride IV on day 1 and oral cyclophosphamide on days 1-7.

GROUP I: Patients receive dexamethasone IV or orally and ondansetron IV on day 1 (prior to each dose of doxorubicin hydrochloride).

GROUP II: Patients receive dexamethasone IV or orally and palonosetron IV on day 1 (prior to each dose of doxorubicin hydrochloride).

Treatment repeats every 7 days for 12-15 courses in the absence of disease progression or unacceptable toxicity.

Intervention(s) in this Clinical Trial

• Drug: palonosetron hydrochloride
  • Given IV
• Drug: cyclophosphamide
  • Given orally
• Drug: dexamethasone
  • Given orally or IV
• Drug: doxorubicin hydrochloride
  • Given IV
• Procedure: quality-of-life assessment
  • Ancillary studies
• Procedure: nausea and vomiting therapy
  • Given IV
• Procedure: management of therapy complications
  • Given IV
• Drug: ondansetron hydrochloride
  • Given IV
• Other: survey administration
  • Ancillary studies

Arms, Groups and Cohorts in this Clinical Trial

• Other: Arm I
  • All patients receive doxorubicin hydrochloride IV on day 1 and oral cyclophosphamide on days 1-7. GROUP I: Patients receive dexamethasone IV or orally and ondansetron IV on day 1 (prior to each dose of doxorubicin hydrochloride). GROUP II: Patients receive dexamethasone IV or orally and palonosetron IV on day 1 (prior to each dose of doxorubicin hydrochloride).

Primary Measures

• Proportion of patients achieving a complete response
  • Time Frame: At 0-24 hours after weekly intravenous doxorubin
    Safety Issue?: No

Secondary Measures

• Proportion of patients achieving complete response
  • Time Frame: At 24-120 hours and 0-120 hours following weekly intravenous doxorubicin
    Safety Issue?: No
• Number of emetic episodes daily
  • Time Frame: At 24-120 hours and 0-120 hours
    Safety Issue?: No
• Time to first emetic episode
  • Time Frame: At 0 hours and continues until first episode
    Safety Issue?: No
• Time to first administration of rescue medication
  • Time Frame: At 0 hours and continues until first administration
    Safety Issue?: No
• Number of doses of rescue medications used
  • Time Frame: Days 1-7 of each cycle
    Safety Issue?: No
• Side effects of antiemetic medications used
  • Time Frame: Days 1-7 of each cycle
    Safety Issue?: No
• Severity of nausea
  • Time Frame: Days 1-7 of each cycle
    Safety Issue?: No
• Quality of life
  • Time Frame: Days 1-7 of each cycle
    Safety Issue?: No

Inclusion Criteria:

• Patients must have a histologically confirmed diagnosis of primary breast carcinoma
• Patient must be naive to chemotherapy at the time of enrollment
• Patients must have prescribed weekly intravenous adriamycin (doxorubicin) and daily oral cyclophosphamide treatment for early breast cancer
• The patient must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
• Patients must have a Karnofsky index of greater than or equal to 50%
• Known mild to moderate hepatic, renal or cardiovascular impairment may be enrolled at the discretion of the investigator

Exclusion Criteria:

• Receipt of investigational drug within 30 days before study entry
• Received any drug with potential anti-emetic effect within 24 hours prior to the start of study-designated chemotherapeutic agent (with the exception of administration of the palonosetron/dexamethasone infusion solution), including the following: 5-HT3 receptor antagonists; dopamine receptor antagonists (metoclopramide); phenothiazine anti-emetics (prochlorperazine, thiethylperazine and perphenazine); diphenhydramine, scopolamine, chlorpheniramine maleate, trimethobenzamide (diphenhydramine will be allowed if given for prophylactic treatment of hypersensitivity reactions associated with the administration of Taxanes); all benzodiazepines; haloperidol, droperidol, tetrahydrocannabinol, or nabilone; any systemic corticosteroid (hydrocortisone, methylprednisolone, prednisone) (topical or inhaled preparations are allowed)
• Any vomiting, retching or NCI Common Toxicity Criteria version 3.0 grade 2-4 nausea in the 24 hours preceding chemotherapy
• Ongoing vomiting from any organic etiology
• Need to receive systemic corticosteroids, except: a) when defined as part of the chemotherapy regimen as a preventative measure for chemotherapy toxicities; b) topical or inhaled preparations; and/or c) when used as rescue medication during the study
• Known contraindication to 5-HT3 receptor antagonists (including palonosetron) or dexamethasone
• Need to receive radiotherapy during the study
• Inability to understand or cooperate with study procedures

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 Investigator: Fred Hutchinson Cancer Research Center Other

Overall Clinical Trial Officials and Contacts

Hannah Linden Principal Investigator Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium  

Information obtained from ClinicalTrials.gov on February 09, 2012

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

Study ID Number: 6140

ClinicalTrials.gov Identifier: NCT00343863

Health Authority: United States: Institutional Review Board