Prevention of Delayed Nausea A Phase III Double-Blind Placebo-Controlled Clinical Trial

Study Overview
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Brief Summary
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RATIONALE: Antiemetic drugs, such as granisetron, dexamethasone, prochlorperazine, aprepitant, and palonosetron, may help lessen or prevent nausea. It is not yet known which combination of antiemetic drugs is more effective in preventing nausea caused by chemotherapy. PURPOSE: This randomized phase III trial is comparing different combinations of granisetron, dexamethasone, prochlorperazine, aprepitant, and palonosetron to see how well they work in preventing nausea in patients undergoing chemotherapy for breast cancer.

Detailed Description
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OBJECTIVES: Primary Compare the efficacy of palonosetron hydrochloride and dexamethasone followed by prochlorperazine with vs without dexamethasone in preventing delayed nausea in women with chemotherapy-naive breast cancer. (Arms I and IV) Determine if palonosetron hydrochloride is more effective than granisetron hydrochloride in controlling treatment-related delayed nausea in these patients. (Arms I and II) Determine if the currently recommended antiemetic guideline of aprepitant combined with palonosetron hydrochloride and dexamethasone is the most effective antiemetic regimen for controlling treatment-related delayed nausea in these patients. (Arms III and IV) Secondary Determine if the addition of dexamethasone to prochlorperazine is more effective than the same regimen without dexamethasone for reducing interference with functioning caused by chemotherapy-induced nausea and vomiting in these patients. (Arms I and IV) Determine if palonosetron hydrochloride is more effective than granisetron hydrochloride for reducing interference with functioning caused by chemotherapy-induced nausea and vomiting in these patients. (Arms I and II) Determine if the currently recommended antiemetic guideline of aprepitant combined with palonosetron hydrochloride and dexamethasone is the most effective antiemetic regimen for reducing interference with functioning due to chemotherapy-induced nausea and vomiting in these patients. (Arms III and IV) OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients are stratified according to CCOP center and gender. Patients are randomized to 1 of 4 treatment arms. Patients receive study treatment approximately 30 minutes before their scheduled first chemotherapy treatment. Arm I: Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3. Arm II: Patients receive granisetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3. Arm III: Patients receive palonosetron hydrochloride IV and dexamethasone IV once on day 1, oral aprepitant once daily on days 1-3, and oral dexamethasone once daily and oral placebo twice daily on days 2 and 3. Arm IV: Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and oral dexamethasone once daily on days 2 and 3. Quality of life is assessed at baseline and on day 4. Nausea and vomiting, fatigue, sleep quality, exercise, and the need for rescue medication (metoclopramide) are assessed on days 1-4. PROJECTED ACCRUAL: A total of 890 patients will be accrued for this study.

Official Title
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Prevention of Delayed Nausea A Phase III Double-Blind Placebo-Controlled Clinical Trial

Conditions
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Nausea

Intervention / Treatment
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* Drug: aprepitant
* Drug: dexamethasone
* Drug: granisetron hydrochloride
* Drug: palonosetron hydrochloride
* Drug: prochlorperazine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Have a diagnosis of cancer and be chemotherapy naive. Must be scheduled to receive a chemotherapy treatment containing doxorubicin hydrochloride, epirubicin hydrochloride, cisplatin, carboplatin, or oxaliplatin (any dose or schedule) without concurrent radiotherapy or interferon treatment Chemotherapy may be for adjuvant, neoadjuvant, curative or palliative intent. Dose-dense regimens (e.g. chemotherapy with doxorubicin or epirubicin given every two weeks)are allowed. For the purposes of this study, Day 1 of chemotherapy will be defined as the day of administration of cisplatin, carboplatin, oxaliplatin, doxorubicin or epirubicin. Regimens with multiple-day doses of doxorubicin, epirubicin, cisplatin, carboplatin, oxaliplatin, dacarbazine, hexamethylmelamine, nitrosoureas, or streptozocin are not allowed. Chemotherapy agents, other than those listed above, may be given orally, intravenously, or by continuous infusion on one or multiple days. Able to understand English Exclusion criteria: No symptomatic brain metastases No concurrent or impending bowel obstruction Regimens containing liposomal doxorubicin or cisplatin are not allowed. No concurrent pimozide, terfenadine, astemizole, or cisapride No concurrent doxorubicin hydrochloride liposome or cisplatin No concurrent multiple-day doses of dacarbazine, altretamine, nitrosoureas, streptozocin, cisplatin, carboplatin, or oxaliplatin

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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I<br>Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3. | Drug: dexamethasone<br>* Given orally or IV<br>* Other names: Decadron;Drug: palonosetron hydrochloride<br>* Given orally or IV<br>* Other names: Aloxi;Drug: prochlorperazine<br>* Given orally or IV<br>* Other names: Compazine;Drug: placebo<br>* Given orally<br>|
| Experimental: Arm II<br>Patients receive granisetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3. | Drug: dexamethasone<br>* Given orally or IV<br>* Other names: Decadron;Drug: granisetron hydrochloride<br>* Given orally or IV<br>* Other names: Kytril;Drug: prochlorperazine<br>* Given orally or IV<br>* Other names: Compazine;Drug: placebo<br>* Given orally<br>|
| Active Comparator: Arm III<br>Patients receive palonosetron hydrochloride IV and dexamethasone IV once on day 1, oral aprepitant once daily on days 1-3, and oral dexamethasone once daily and oral placebo twice daily on days 2 and 3. | Drug: aprepitant<br>* Given orally or IV<br>* Other names: Emend;Drug: dexamethasone<br>* Given orally or IV<br>* Other names: Decadron;Drug: palonosetron hydrochloride<br>* Given orally or IV<br>* Other names: Aloxi;Drug: placebo<br>* Given orally<br>|
| Experimental: Arm IV<br>Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and oral dexamethasone once daily on days 2 and 3. | Drug: dexamethasone<br>* Given orally or IV<br>* Other names: Decadron;Drug: palonosetron hydrochloride<br>* Given orally or IV<br>* Other names: Aloxi;Drug: prochlorperazine<br>* Given orally or IV<br>* Other names: Compazine;Drug: placebo<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Home Record: Severity of Delayed Nausea | 1=not at all nauseated to 7=extremely nauseated, therefore higher values are worse | average of day 1 afternoon, evening and night, and all of days 2 and 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nausea and vomiting, recurrent breast cancer, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, inflammatory breast cancer, male breast cancer