Emend for Multiple-day Emetogenic Chemotherapy

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

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.

Study Overview

• Status: Completed
• Conditions: Nausea; Vomiting
• Intervention / Treatment: Drug: aprepitant, ondansetron, dexamethasone

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Single arm study with Emend; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Collaborators: Merck Sharp & Dohme LLC; Northwestern Memorial Hospital
• Investigators: Principal Investigator: Stacy Shord, PharmD, University of Illinois at Chicago

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (ACTUAL): November 1, 2008
• Study Completion (ACTUAL): January 1, 2009

Study Registration Dates

• First Submitted: July 3, 2008
• First Submitted That Met QC Criteria: July 8, 2008
• First Posted (ESTIMATE): July 9, 2008

Study Record Updates

• Last Update Posted (ACTUAL): August 4, 2021
• Last Update Submitted That Met QC Criteria: August 2, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: chemotherapy; nausea; vomiting; corticosteroids; aprepitant; rescue therapy; multiple days; serotonin receptor antagonist
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Neurokinin-1 Receptor Antagonists; Dexamethasone; Ondansetron; Aprepitant
• Other Study ID Numbers: 2005-0363 (Other Identifier: M D Anderson Cancer Center)