Male Breast Cancer, Nausea and Vomiting, Stage I Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer
Conditions
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
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.
Interventions
Given IV
DRUGcyclophosphamide
Given orally
DRUGdexamethasone
Given orally or IV
DRUGdoxorubicin hydrochloride
Given IV
PROCEDUREquality-of-life assessment
Ancillary studies
PROCEDUREnausea and vomiting therapy
Given IV
PROCEDUREmanagement of therapy complications
Given IV
Given IV
OTHERsurvey administration
Ancillary studies
Sponsors
National Cancer Institute (NCI)
University of Washington
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Count of Patients Achieving a Complete Response | At 0-24 hours after weekly intravenous doxorubin |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days With Emetic Episodes and Rescue Medicines | Up to 3 months | — |
| 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 |
| 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 |
| Count of Patients Achieving Complete Response | At 24-120 hours after weekly intravenous doxorubicin | — |
| Side Effects of Antiemetic Medications Used | Up to 3 months | — |
| Severity of Nausea | Up to 3 months | Count of participants with severe nausea |
| Quality of Life | Up to 3 months | — |
| Number of Doses of Rescue Medications Used | Days 1-7 of each cycle | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dexamethasone + Ondansetron IV 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). | 7 |
| Dexamethasone + Palonosetron IV 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). | 34 |
| Total | 41 |
Baseline characteristics
| Characteristic | Dexamethasone + Palonosetron IV | Total | Dexamethasone + Ondansetron IV |
|---|---|---|---|
| Age, Continuous | 49 years | 50 years | 54 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 36 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 31 Participants | 37 Participants | 6 Participants |
| Sex: Female, Male Female | 34 Participants | 41 Participants | 7 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 7 | 15 / 34 |
| serious Total, serious adverse events | 0 / 7 | 0 / 34 |
Outcome results
Primary
Count of Patients Achieving a Complete Response
Time frame: At 0-24 hours after weekly intravenous doxorubin
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexamethasone + Ondansetron IV | Count of Patients Achieving a Complete Response | 3 Participants |
| Dexamethasone + Palonosetron IV | Count of Patients Achieving a Complete Response | 15 Participants |
Secondary
Count of Patients Achieving Complete Response
Time frame: At 24-120 hours after weekly intravenous doxorubicin
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexamethasone + Ondansetron IV | Count of Patients Achieving Complete Response | 3 Participants |
| Dexamethasone + Palonosetron IV | Count of Patients Achieving Complete Response | 15 Participants |
Secondary
Number of Days With Emetic Episodes and Rescue Medicines
Time frame: Up to 3 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dexamethasone + Ondansetron IV | Number of Days With Emetic Episodes and Rescue Medicines | Vomiting during neoadjuvant chemotherapy | 0 days |
| Dexamethasone + Ondansetron IV | Number of Days With Emetic Episodes and Rescue Medicines | Took rescue medicines | 2 days |
| Dexamethasone + Palonosetron IV | Number of Days With Emetic Episodes and Rescue Medicines | Vomiting during neoadjuvant chemotherapy | 0 days |
| Dexamethasone + Palonosetron IV | Number of Days With Emetic Episodes and Rescue Medicines | Took rescue medicines | 9.5 days |
Secondary
Number of Doses of Rescue Medications Used
Time frame: Days 1-7 of each cycle
Population: Patients were unable to consistently complete this part of the FLIE questionnaire and thus we did not retain data from any of the participants.
Secondary
Number of Participants That Had Emesis Within 48 Hours of Chemotherapy
Count of patients that had emesis within 48 hours of chemotherapy
Time frame: Up to 48 hours of chemotherapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexamethasone + Ondansetron IV | Number of Participants That Had Emesis Within 48 Hours of Chemotherapy | 0 Participants |
| Dexamethasone + Palonosetron IV | Number of Participants That Had Emesis Within 48 Hours of Chemotherapy | 1 Participants |
Secondary
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
Time frame: up to 48 hours of chemotherapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexamethasone + Ondansetron IV | Number of Participants That Had First Administration of Rescue Medication Within 48 Hours | 1 Participants |
| Dexamethasone + Palonosetron IV | Number of Participants That Had First Administration of Rescue Medication Within 48 Hours | 4 Participants |
Secondary
Quality of Life
Time frame: Up to 3 months
| Arm | Measure | Group | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|---|
| Dexamethasone + Ondansetron IV | Quality of Life | FLIE Nausea | High impact (<36) | 4 FLIE questionnaires |
| Dexamethasone + Ondansetron IV | Quality of Life | FLIE Nausea | Medium impact (36-54) | 5 FLIE questionnaires |
| Dexamethasone + Ondansetron IV | Quality of Life | FLIE Nausea | No impact of daily life (>54) | 26 FLIE questionnaires |
| Dexamethasone + Ondansetron IV | Quality of Life | FLIE Vomiting | High impact (<36) | 1 FLIE questionnaires |
| Dexamethasone + Ondansetron IV | Quality of Life | FLIE Vomiting | Medium impact (36-54) | 3 FLIE questionnaires |
| Dexamethasone + Ondansetron IV | Quality of Life | FLIE Vomiting | No impact of daily life (>54) | 31 FLIE questionnaires |
| Dexamethasone + Palonosetron IV | Quality of Life | FLIE Vomiting | Medium impact (36-54) | 9 FLIE questionnaires |
| Dexamethasone + Palonosetron IV | Quality of Life | FLIE Nausea | High impact (<36) | 44 FLIE questionnaires |
| Dexamethasone + Palonosetron IV | Quality of Life | FLIE Vomiting | High impact (<36) | 10 FLIE questionnaires |
| Dexamethasone + Palonosetron IV | Quality of Life | FLIE Nausea | Medium impact (36-54) | 74 FLIE questionnaires |
| Dexamethasone + Palonosetron IV | Quality of Life | FLIE Vomiting | No impact of daily life (>54) | 347 FLIE questionnaires |
| Dexamethasone + Palonosetron IV | Quality of Life | FLIE Nausea | No impact of daily life (>54) | 248 FLIE questionnaires |
Secondary
Severity of Nausea
Count of participants with severe nausea
Time frame: Up to 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexamethasone + Ondansetron IV | Severity of Nausea | 1 Participants |
| Dexamethasone + Palonosetron IV | Severity of Nausea | 4 Participants |
Secondary
Side Effects of Antiemetic Medications Used
Time frame: Up to 3 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dexamethasone + Ondansetron IV | Side Effects of Antiemetic Medications Used | Headaches | 0 Participants |
| Dexamethasone + Ondansetron IV | Side Effects of Antiemetic Medications Used | Constipation | 2 Participants |
| Dexamethasone + Palonosetron IV | Side Effects of Antiemetic Medications Used | Constipation | 15 Participants |
| Dexamethasone + Palonosetron IV | Side Effects of Antiemetic Medications Used | Headaches | 2 Participants |