Clinical trial NCT00711555: Emend for Multiple-day Emetogenic Chemotherapy
Official title: An Open Label Phase II Study of Aprepitant for Multi-day Moderately-high to Highly Emetogenic Chemotherapy Regimens
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nausea
Vomiting
Keywords: nausea
vomiting
multiple days
chemotherapy
serotonin receptor antagonist
corticosteroids
aprepitant
rescue therapy
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
name: Northwestern Memorial Hospital
First posted: 2008-07-09
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Complete Response (Percentage of Patients)
timeFrame: cycle 1, day 1
Secondary outcomes:
measure: Complete Protection
timeFrame: cycle 1, day 1
measure: no Emesis
timeFrame: cycle 1, day 1
measure: no Nausea
timeFrame: cycle 1, day 1
measure: no Significant Nausea
timeFrame: cycle 1, day 1
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois Medical Center
state: Illinois
Study officials:
affiliation: University of Illinois at Chicago
name: Stacy Shord, PharmD
role: PRINCIPAL_INVESTIGATOR
References: