Emend for Multiple-day Emetogenic Chemotherapy

Study Overview
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Brief Summary
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The purpose of the study is to assess the effect of Emend (aprepitant) on nausea and vomiting associated with chemotherapy. Chemotherapy commonly causes nausea and vomiting and this affects patients' quality of life and attitudes toward treatment. Although nausea and vomiting associated with chemotherapy has been decreasing due to improved therapy, some patients will still experience this side effect. Therefore, new medications are needed to decrease the amount of nausea and vomiting patients have with chemotherapy. Emend (aprepitant) is a new medication used to treat nausea and vomiting with chemotherapy, but it has only been studied in patients receiving only one dose of chemotherapy that makes most people sick. However, there is little experience with this medication in patients receiving multiple days of chemotherapy that causes nausea and vomiting.

Detailed Description
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In the studies leading to aprepitant's approval, subjects received only one dose of highly emetogenic chemotherapy. Campos et al studied subjects who received their first course of cisplatin containing chemotherapy that included a cisplatin dose 70mg/m2 and reported that aprepitant in addition to granisetron and dexamethasone increased the number of subjects without acute or delayed emesis (p<0.01). A similar study done by Poli-Bigelli et al indicated that adding aprepitant to a standard antiemetic regimen increased the percentage of subjects without emesis and using rescue therapy during the acute phase (83% to 69%; p < 0.001). Adding aprepitant also increased the percentage of subjects with no emesis or use of rescue medications in the delayed phase (68% vs. 47%, p<0.001). Although these studies demonstrate the benefits of aprepitant for a one day chemotherapy regimen, the benefits of adding aprepitant to current standard antiemetic therapy (dexamethasone plus a serotonin receptor antagonist) in subjects receiving multiple days of moderately-high to highly emetogenic chemotherapy have not been examined within a clinical study. We hypothesize that aprepitant with dexamethasone and a serotonin receptor antagonist from days one to two days after finishing chemotherapy will decrease nausea for subjects receiving chemotherapy regimens that include multiple days of treatment with moderately-high to highly emetogenic chemotherapy.

Official Title
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An Open Label Phase II Study of Aprepitant for Multi-day Moderately-high to Highly Emetogenic Chemotherapy Regimens

Conditions
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Nausea, Vomiting

Intervention / Treatment
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* Drug: aprepitant, ondansetron, dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with a life expectancy > 3 months Subjects with an ECOG performance score < 3 Subjects with access to a telephone for follow-up Subjects able to swallow tablets and capsules Exclusion Criteria: Subjects who previously received aprepitant as prophylaxis for chemotherapy induced nausea and vomiting. Subjects with an allergy, hypersensitivity, or contraindication to aprepitant, dexamethasone, prochlorperazine or a serotonin receptor antagonist. Subject with uncontrolled diabetes or a concurrent illness/condition requiring chronic systemic steroids or pre-existing gastrointestinal pathology. Subjects with a history of excessive alcohol consumption. Women who are pregnant or lactating. Subjects with nausea at baseline or chronically using other antiemetic agent(s). Subjects currently receiving another investigational agent. Subjects taking a medication that can interact with aprepitant, including the following medications: warfarin oral contraceptives tolbutamide phenytoin midazolam ketoconazole rifampin paroxetine diltiazem Subjects with poor hepatic or renal function defined as AST > 3 x ULN, ALT > 3 x ULN, total bilirubin > 3 x ULN, alkaline phosphatase > 3 x ULN or serum creatinine >2 mg/dl measured within three months before starting chemotherapy. Subjects with hepatic metastases with AST > 5 x ULN, ALT > 5 x ULN, total bilirubin > 5 x ULN, alkaline phosphatase > 5 x ULN.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm study with Emend<br>On day 1, the subject will receive a total daily dose of oral dexamethasone 12mg, oral ondansetron 24mg, and oral aprepitant 125mg. On days 2 to THE LAST DAY OF THE MODERATELY-HIGH TO HIGHLY EMETOGENIC CHEMOTHERAPY, subjects will receive a total daily dose of oral dexamethasone 12mg, oral ondansetron 24mg, and oral aprepitant 80mg. All anti-emetics should be give one hour before starting chemotherapy administration. FOR TWO DAYS AFTER RECEIVING CHEMOTHERAPY, the subject will be prescribed oral dexamethasone 4mg every 12 hours and oral aprepitant 80 mg every day. | Drug: aprepitant, ondansetron, dexamethasone<br>* On day 1, the subject will receive a total daily dose of oral dexamethasone 12mg, oral ondansetron 24mg, and oral aprepitant 125mg. On days 2 to THE LAST DAY OF THE MODERATELY-HIGH TO HIGHLY EMETOGENIC CHEMOTHERAPY, subjects will receive a total daily dose of oral dexamethasone 12mg, oral ondansetron 24mg, and oral aprepitant 80mg. All anti-emetics should be give one hour before starting chemotherapy administration. FOR TWO DAYS AFTER RECEIVING CHEMOTHERAPY, the subject will be prescribed oral dexamethasone 4mg every 12 hours and oral aprepitant 80 mg every day. FOR RESCUE, the subject will be prescribed prochlorperazine 10 mg oral every 4 hours as needed for nausea and prochlorperazine 10 mg intravenous every 4 hours as needed for vomiting.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response (Percentage of Patients) | defined as a no emetic episodes and no use of rescue therapy | cycle 1, day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Protection | defined as no emesis, no use of rescue medications, and a maximum nausea severity < 25 mm (100 mm visual analog scale, 0 = no nausea, 100 = worst nausea) | cycle 1, day 1 | 
| no Emesis |  | cycle 1, day 1 | 
| no Nausea | defined as maximum nausea severity < 5 mm (100 mm visual analog scale, 0 = no nausea, 100 = worst nausea) | cycle 1, day 1 | 
| no Significant Nausea | defined as a maximum nausea severity < 25 mm (100 mm visual analog scale, 0 = no nausea, 100 = worst nausea) | cycle 1, day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nausea, vomiting, multiple days, chemotherapy, serotonin receptor antagonist, corticosteroids, aprepitant, rescue therapy