Phase 2B Double Blind Placebo Controlled Crossover Study Evaluating the Efficacy of IV Fosaprepitant for Chemo Induced N/V With High Dose Interleukin 2 for Metastatic Melanoma and Metastatic Renal Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Number of Patients With Complete Response During Inpatient Admission
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
- •Evidence of a personally signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial.
- •Subjects who are willing to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- •Be at least 18 years of age at the time of informed consent.
- •Has a diagnosis of metastatic melanoma or metastatic renal cell carcinoma and who will undergo high-dose interleukin-2 (HD IL-2) therapy
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less at Baseline/Day 1 visit. (See Appendix 6 on p. 51, ECOG Performance Status)
- •Female of reproductive potential must agree use non-hormonal methods to avoid pregnancy during study participation and for 1 month after last dose of study drug
排除标准
- •Subjects presenting with any of the following will not be included in the study:
- •Women who are pregnant or lactating, or planning pregnancy
- •Women of childbearing potential who refuse to use non-hormonal methods to avoid pregnancy
- •Known hypersensitivity to any component of fosaprepitant or aprepitant
- •Have taken pimozide or cisapride <4 weeks, cytochrome P450 3A4 inducers within 30 days, strong CYP3A4 inhibitors within 7 days, or antiemetics within 48 hours prior to treatment initiation (See Appendix 7 on p. 52 for list of CYP3A4 inducers and strong CYP3A4 inhibitors)
- •Have evidence of clinically significant and unstable diseases or conditions such as cardiovascular, immunosuppressive, hematologic, hepatic, neurologic, renal, endocrine, collagen-vascular, or gastrointestinal abnormalities that the investigator thinks may interfere with study participation
- •Participation in other study using an investigational or experimental therapy or procedure within 4 weeks or 5 half-lives (whichever is longer) before study entry
- •Subjects cannot participate in studies of other investigational or experimental therapies or procedures at any time during their participation in this study.
- •Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
- •Subjects who are investigational site staff members or who are Sponsor employees directly involved in the conduct of the trial.
- •A subject who, in the opinion of the investigator or sponsor, will be uncooperative or unable to comply with study procedures.
研究组 & 干预措施
Placebo
During placebo admission, intravenous 0.9% saline every 48 hours during 6-day hospital admission
干预措施: Fosaprepitant (Drug)
Fosaprepitant
During treatment admission, intravenous fosaprepitant 150 mg every 48 hours during 6-day hospital admission
干预措施: Fosaprepitant (Drug)
结局指标
主要结局
Number of Patients With Complete Response During Inpatient Admission
时间窗: From the initiation of through 48 hours following the final dose of Interleukin-2
No vomiting from the initiation of through 48 hours following the final dose of HD IL-2
次要结局
未报告次要终点
研究者
John Richart, M.D.
Associate Professor, Dept. of Internal Medicine, Hematology and Oncology
St. Louis University