Clinical trial NCT01874119
Conditions: Chemotherapy-induced Nausea and Vomiting
Keywords: melanoma renal cell carcinoma interleukin-2
Sponsor: St. Louis University
Start date: 2013-09-01; Completion date: 2015-12-03
Enrollment: 13 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purpose of this study is to investigate the effectiveness of intravenous fosaprepitant therapy to reduce nausea and vomiting during the treatment of high dose interleukin-2 (HD IL-2) therapy for metastatic melanoma or metastatic renal cell carcinoma. Fosaprepitant is an intravenous (IV) medication that is FDA- approved for use in adults for the prevention of nausea and vomiting during chemotherapy. Fosaprepitant works by blocking the neurokinin-1 receptor, which is a receptor in the brain that is known to cause nausea and vomiting. Past studies estimate that up to 70% of patients undergoing treatment with HD IL-2 will have nausea and/or vomiting. While fosaprepitant has been used in clinical practice to treat nausea and vomiting during HD IL-2, there have not been any studies done to see how well it works. All patients will receive treatment (IV fosaprepitant) during the study during either the first or second hospital admission for HD IL-2. On the admission that the subject is not receiving IV fosaprepitant, the subject will receive placebo (a medicine that looks like fosaprepitant, but is not active). The study is double-blinded, which means neither the subject, nor the study doctor will know to which group you have been assigned to that admission (IV fosaprepitant or placebo). This study design was chosen to limit the potential for bias, which means the trial was designed to try to ensure that unknown factors do not affect trial results. When patients start the study, patients will be randomly assigned to one of two groups: those who receive treatment (IV fosaprepitant) first and those who receive placebo first. During the first admission, subjects will be given the IV fosaprepitant or IV placebo during admission. During the second admission, subjects will 'crossover' and receive the other treatment that they did not receive during the first admission. Improvement in nausea and vomiting will be assessed by counting the number of nausea and vomiting episodes, recording if the subject needs additional medication for nausea and vomiting, and by using patient questionnaires.

Detailed description:
This is a Phase 2B double-blind placebo-controlled crossover study evaluating the efficacy of intravenous fosaprepitant for chemotherapy-induced nausea and vomiting in patients undergoing high-dose interleukin-2 (HD IL-2) therapy (720,000 IU/kg per dose intravenously; 14 doses, 2 cycles per course) for metastatic melanoma and metastatic renal cell carcinoma. A total of 22 subjects will be enrolled in the study. On study entry, patients will be randomized to receive either IV fosaprepitant (150 mg on Day 1, Day 3, or Day 5) or matched placebo during first admission of HD IL-2 therapy (cycle 1). All subjects will crossover and receive the opposite treatment during cycle 2. All patients will receive ondansetron 24 mg by mouth daily per standard protocol every 24 hours during Days 1-5 of admission starting 30 minutes prior to first dose of HD IL-2. During the treatment phase, subjects will receive Patients will receive IV fosaprepitant 30 minutes before first dose of HD IL-2 therapy and every 48 hours until completion of HD IL-2 therapy. Upon study entry, the subjects will be given a dairy to report episodes of vomiting, use of rescue therapy, and nausea assessments using the 1-100 scale within the visual analogue scale (VAS). The subject will be instructed to complete entries from baseline assessment (prior to first dose) until 5 days after last dose of HD IL-2 for endpoint analysis. During inpatient admissions, subjects will complete diary entries before each dose (q8 hours). As an outpatient, subjects will complete diary entries on a daily basis. Recording of whether or not pruritus was observed will also be collected within the subject diary. If a patient reports pruritus, the severity of pruritus on the 1-100 scale visual analogue scale (VAS) will also be collected. The study team will record any episodes of vomiting and the use of rescue therapy and ensure completion of patient diary during inpatient portion. Assessments will be made via telephone contact to determine onset of any episodes of CINV during outpatient portion. Safety assessments including adverse events (AEs) monitoring will be performed and assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Arms: arm 1: During treatment admission, intravenous fosaprepitant 150 mg every 48 hours during 6-day hospital admission arm 2: During placebo admission, intravenous 0.9% saline every 48 hours during 6-day hospital admission
Interventions: intervention 1: Fosaprepitant
Intervention descriptions: intervention 1: During treatment admission, intravenous fosaprepitant 150 mg every 48 hours during 6-day hospital admission

Protocol documents: