Phase 2B Double-blind Placebo-controlled Crossover Study Evaluating the Efficacy of Intravenous Fosaprepitant for Chemotherapy-induced Nausea and Vomiting (CINV) Associated With High-dose Interleukin-2 (HD IL-2) for Metastatic Melanoma and Metastatic Renal Cell Carcinoma
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.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Complete response during inpatient admission
No vomiting during inpatient admissions
John M Richart, M.D.
Saint Louis University, Department of Internal Medicine, Division of Hematology and Oncology
United States: Food and Drug Administration
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