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

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT00343863
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 41
• Location: 1
• Arms: 2
• Duration (Months): 59
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Male Breast Cancer; Nausea and Vomiting; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer	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	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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.

2. 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.

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

4. 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).

5. 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 Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• 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
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

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).	Drug: cyclophosphamide; Given orally; Other Names: CPM CTX Cytoxan Endoxan Endoxana ; Drug: dexamethasone; Given orally or IV; Other Names: Aeroseb-Dex Decaderm Decadron DM DXM ; Drug: doxorubicin hydrochloride; Given IV; Other Names: ADM ADR Adria Adriamycin PFS Adriamycin RDF ; Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment ; 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: GR 38032F GR-C507/75 SN-307 Zofran ; Other: survey administration; Ancillary studies
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).	Drug: palonosetron hydrochloride; Given IV; Other Names: Aloxi RS 25259-197 ; Drug: cyclophosphamide; Given orally; Other Names: CPM CTX Cytoxan Endoxan Endoxana ; Drug: dexamethasone; Given orally or IV; Other Names: Aeroseb-Dex Decaderm Decadron DM DXM ; Drug: doxorubicin hydrochloride; Given IV; Other Names: ADM ADR Adria Adriamycin PFS Adriamycin RDF ; Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment ; 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 ; Other: survey administration; Ancillary studies

Outcome Measures

Primary Outcome Measures

1. Count of Patients Achieving a Complete Response [At 0-24 hours after weekly intravenous doxorubin]

Secondary Outcome Measures

1. Count of Patients Achieving Complete Response [At 24-120 hours after weekly intravenous doxorubicin]

2. Number of Days With Emetic Episodes and Rescue Medicines [Up to 3 months]

3. Number of Participants That Had Emesis Within 48 Hours of Chemotherapy [Up to 48 hours of chemotherapy]

   Count of patients that had emesis within 48 hours of chemotherapy

4. Number of Participants That Had First Administration of Rescue Medication Within 48 Hours [up to 48 hours of chemotherapy]

   Count of patients that had first administration of rescue medication within 48 Hours

5. Number of Doses of Rescue Medications Used [Days 1-7 of each cycle]

6. Side Effects of Antiemetic Medications Used [Up to 3 months]

7. Severity of Nausea [Up to 3 months]

   Count of participants with severe nausea

8. Quality of Life [Up to 3 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• University of Washington
• National Cancer Institute (NCI)

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hannah Linden, Principal Investigator, University of Washington
• ClinicalTrials.gov Identifier: NCT00343863
• Other Study ID Numbers: 6140; NCI-2010-00801
• First Posted: Jun 23, 2006
• Last Update Posted: Jul 11, 2017
• Last Verified: Jun 1, 2017

• Additional relevant MeSH terms: Breast Neoplasms; Breast Neoplasms, Male; Nausea; Vomiting; Dexamethasone; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Ondansetron; Palonosetron; Antiemetics

Study Results

Participant Flow

Arm/Group Title	Dexamethasone + Ondansetron IV	Dexamethasone + Palonosetron IV
Arm/Group Description	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).	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).
Period Title: Overall Study
STARTED	7	34
COMPLETED	7	34
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Dexamethasone + Ondansetron IV	Dexamethasone + Palonosetron IV	Total
Arm/Group Description	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).	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).	Total of all reporting groups
Overall Participants	7	34	41
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	54	49	50
Sex: Female, Male (Count of Participants)
Female	7 100%	34 100%	41 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 14.3%	2 5.9%	3 7.3%
Not Hispanic or Latino	6 85.7%	30 88.2%	36 87.8%
Unknown or Not Reported	0 0%	2 5.9%	2 4.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 14.3%	0 0%	1 2.4%
Asian	0 0%	1 2.9%	1 2.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	6 85.7%	31 91.2%	37 90.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 5.9%	2 4.9%

Outcome Measures

1. Primary Outcome

Title	Count of Patients Achieving a Complete Response
Time Frame	At 0-24 hours after weekly intravenous doxorubin

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexamethasone + Ondansetron IV	Dexamethasone + Palonosetron IV
Arm/Group Description	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).	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).
Measure Participants	7	34
Count of Participants [Participants]	3 42.9%	15 44.1%

2. Secondary Outcome

Title	Count of Patients Achieving Complete Response
Time Frame	At 24-120 hours after weekly intravenous doxorubicin

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexamethasone + Ondansetron IV	Dexamethasone + Palonosetron IV
Arm/Group Description	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).	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).
Measure Participants	7	34
Count of Participants [Participants]	3 42.9%	15 44.1%

3. Secondary Outcome

Title	Number of Days With Emetic Episodes and Rescue Medicines
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexamethasone + Ondansetron IV	Dexamethasone + Palonosetron IV
Arm/Group Description	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).	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).
Measure Participants	7	34
Vomiting during neoadjuvant chemotherapy	0	0
Took rescue medicines	2	9.5

4. Secondary Outcome

Title	Number of Participants That Had Emesis Within 48 Hours of Chemotherapy
Description	Count of patients that had emesis within 48 hours of chemotherapy
Time Frame	Up to 48 hours of chemotherapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexamethasone + Ondansetron IV	Dexamethasone + Palonosetron IV
Arm/Group Description	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).	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).
Measure Participants	7	34
Count of Participants [Participants]	0 0%	1 2.9%

5. Secondary Outcome

Title	Number of Participants That Had First Administration of Rescue Medication Within 48 Hours
Description	Count of patients that had first administration of rescue medication within 48 Hours
Time Frame	up to 48 hours of chemotherapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexamethasone + Ondansetron IV	Dexamethasone + Palonosetron IV
Arm/Group Description	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).	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).
Measure Participants	7	34
Count of Participants [Participants]	1 14.3%	4 11.8%

6. Secondary Outcome

Title	Number of Doses of Rescue Medications Used
Time Frame	Days 1-7 of each cycle

Outcome Measure Data

Analysis Population Description

Patients were unable to consistently complete this part of the FLIE questionnaire and thus we did not retain data from any of the participants.

Arm/Group Title	Dexamethasone + Ondansetron IV	Dexamethasone + Palonosetron IV
Arm/Group Description	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).	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).
Measure Participants	0	0

7. Secondary Outcome

Title	Side Effects of Antiemetic Medications Used
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexamethasone + Ondansetron IV	Dexamethasone + Palonosetron IV
Arm/Group Description	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).	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).
Measure Participants	7	34
Constipation	2 28.6%	15 44.1%
Headaches	0 0%	2 5.9%

8. Secondary Outcome

Title	Severity of Nausea
Description	Count of participants with severe nausea
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexamethasone + Ondansetron IV	Dexamethasone + Palonosetron IV
Arm/Group Description	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).	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).
Measure Participants	7	34
Count of Participants [Participants]	1 14.3%	4 11.8%

9. Secondary Outcome

Title	Quality of Life
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dexamethasone + Ondansetron IV	Dexamethasone + Palonosetron IV
Arm/Group Description	Patients receive dexamethasone IV or orally and ondansetron IV on day 1 (prior to each dose of doxorubicin hydrochloride).	Patients receive dexamethasone IV or orally and palonosetron IV on day 1 (prior to each dose of doxorubicin hydrochloride).
Measure Participants	7	34
Measure FLIE questionnaires	35	366
High impact (<36)	4	44
Medium impact (36-54)	5	74
No impact of daily life (>54)	26	248
High impact (<36)	1	10
Medium impact (36-54)	3	9
No impact of daily life (>54)	31	347

Adverse Events

Arm/Group Title	Dexamethasone + Ondansetron IV		Dexamethasone + Palonosetron IV
Arm/Group Description	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).		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).
All Cause Mortality
	Dexamethasone + Ondansetron IV		Dexamethasone + Palonosetron IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dexamethasone + Ondansetron IV		Dexamethasone + Palonosetron IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/34 (0%)
Other (Not Including Serious) Adverse Events
	Dexamethasone + Ondansetron IV		Dexamethasone + Palonosetron IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/7 (28.6%)		15/34 (44.1%)
Gastrointestinal disorders
Constipation	2/7 (28.6%)		15/34 (44.1%)
General disorders
Headache	0/7 (0%)		2/34 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.