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

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

Study Overview

• Status: Completed
• Conditions: Stage I Breast Cancer; Male Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Nausea and Vomiting
• Intervention / Treatment: Procedure: quality-of-life assessment; Drug: doxorubicin hydrochloride; Other: survey administration; Drug: cyclophosphamide; Drug: dexamethasone; Procedure: nausea and vomiting therapy; Procedure: management of therapy complications; Drug: ondansetron hydrochloride; Drug: palonosetron hydrochloride

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dexamethasone + Ondansetron IV on Day 1; 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).	Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment; Drug: doxorubicin hydrochloride; Given IV; Other Names: ADM; Adriamycin PFS; Adriamycin RDF; ADR; Adria; Other: survey administration; Ancillary studies; Drug: cyclophosphamide; Given orally; Other Names: Cytoxan; Endoxan; CPM; CTX; Endoxana; Drug: dexamethasone; Given orally or IV; Other Names: Aeroseb-Dex; Decaderm; Decadron; DM; DXM; Procedure: nausea and vomiting therapy; Given IV; Other Names: antiemetic support; management of nausea and vomiting; nausea and vomiting management; therapy, nausea and vomiting; vomiting and nausea management; Procedure: management of therapy complications; Given IV; Other Names: complications of therapy, management of; Drug: ondansetron hydrochloride; Given IV; Other Names: Zofran; GR 38032F; GR-C507/75; SN-307
Experimental: Dexamethasone + Palonosetron IV on Day 1; 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).	Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment; Drug: doxorubicin hydrochloride; Given IV; Other Names: ADM; Adriamycin PFS; Adriamycin RDF; ADR; Adria; Other: survey administration; Ancillary studies; Drug: cyclophosphamide; Given orally; Other Names: Cytoxan; Endoxan; CPM; CTX; Endoxana; Drug: dexamethasone; Given orally or IV; Other Names: Aeroseb-Dex; Decaderm; Decadron; DM; DXM; Procedure: nausea and vomiting therapy; Given IV; Other Names: antiemetic support; management of nausea and vomiting; nausea and vomiting management; therapy, nausea and vomiting; vomiting and nausea management; Procedure: management of therapy complications; Given IV; Other Names: complications of therapy, management of; Drug: palonosetron hydrochloride; Given IV; Other Names: Aloxi; RS 25259-197

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: June 22, 2006
• First Submitted That Met QC Criteria: June 22, 2006
• First Posted (Estimate): June 23, 2006

Study Record Updates

• Last Update Posted (Actual): July 11, 2017
• Last Update Submitted That Met QC Criteria: June 10, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Signs and Symptoms, Digestive; Breast Diseases; Breast Neoplasms; Nausea; Vomiting; Breast Neoplasms, Male; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antibiotics, Antineoplastic; Serotonin 5-HT3 Receptor Antagonists; Antipruritics; Dexamethasone; Cyclophosphamide; Palonosetron; Doxorubicin; Liposomal doxorubicin; Ondansetron; Antiemetics
• Other Study ID Numbers: 6140 (Other Identifier: Faculty of Medicine, Zagazig University); NCI-2010-00801 (Registry Identifier: CTRP (Clinical Trial Reporting Program))