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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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

Conditions
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Male Breast Cancer, Nausea and Vomiting, Stage I Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer

Intervention / Treatment
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* Drug: palonosetron hydrochloride
* Drug: cyclophosphamide
* Drug: dexamethasone
* Drug: doxorubicin hydrochloride
* Procedure: quality-of-life assessment
* Procedure: nausea and vomiting therapy
* Procedure: management of therapy complications
* Drug: ondansetron hydrochloride
* Other: survey administration


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dexamethasone + Ondansetron IV on Day 1<br>All patients receive doxorubicin hydrochloride IV on day 1 and oral cyclophosphamide on days 1-7. Patients receive dexamethasone IV or orally and ondansetron IV on day 1 (prior to each dose of doxorubicin hydrochloride). | Drug: cyclophosphamide<br>* Given orally<br>* Other names: Endoxana;Drug: dexamethasone<br>* Given orally or IV<br>* Other names: DXM;Drug: doxorubicin hydrochloride<br>* Given IV<br>* Other names: Adriamycin RDF;Procedure: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;Procedure: nausea and vomiting therapy<br>* Given IV<br>* Other names: vomiting and nausea management;Procedure: management of therapy complications<br>* Given IV<br>* Other names: complications of therapy, management of;Drug: ondansetron hydrochloride<br>* Given IV<br>* Other names: Zofran;Other: survey administration<br>* Ancillary studies<br>|
| Experimental: Dexamethasone + Palonosetron IV on Day 1<br>All patients receive doxorubicin hydrochloride IV on day 1 and oral cyclophosphamide on days 1-7. Patients receive dexamethasone IV or orally and palonosetron IV on day 1 (prior to each dose of doxorubicin hydrochloride). | Drug: palonosetron hydrochloride<br>* Given IV<br>* Other names: RS 25259-197;Drug: cyclophosphamide<br>* Given orally<br>* Other names: Endoxana;Drug: dexamethasone<br>* Given orally or IV<br>* Other names: DXM;Drug: doxorubicin hydrochloride<br>* Given IV<br>* Other names: Adriamycin RDF;Procedure: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;Procedure: nausea and vomiting therapy<br>* Given IV<br>* Other names: vomiting and nausea management;Procedure: management of therapy complications<br>* Given IV<br>* Other names: complications of therapy, management of;Other: survey administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of Patients Achieving a Complete Response |  | At 0-24 hours after weekly intravenous doxorubin | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of Patients Achieving Complete Response |  | At 24-120 hours after weekly intravenous doxorubicin | 
| Number of Days With Emetic Episodes and Rescue Medicines |  | Up to 3 months | 
| Number of Participants That Had Emesis Within 48 Hours of Chemotherapy | Count of patients that had emesis within 48 hours of chemotherapy | Up to 48 hours of chemotherapy | 
| Number of Participants That Had First Administration of Rescue Medication Within 48 Hours | Count of patients that had first administration of rescue medication within 48 Hours | up to 48 hours of chemotherapy | 
| Number of Doses of Rescue Medications Used |  | Days 1-7 of each cycle | 
| Side Effects of Antiemetic Medications Used |  | Up to 3 months | 
| Severity of Nausea | Count of participants with severe nausea | Up to 3 months | 
| Quality of Life |  | Up to 3 months |