A Randomized Open Label Phase II Trial of Aprepitant (Emend) in Combination With Ondansetron Compared to Standard 5HT3 Serotonin Antagonist (Ondansetron) in the Prevention of Acute and Delayed Chemotherapy Induced Nausea and Vomiting (CINV) in Glioma Patients Receiving a Temozolomide Based Regimen
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 136
- 试验地点
- 1
- 主要终点
- Proportion of Patients Achieving Complete Control (CC)
研究概览
简要总结
Patients diagnosed with malignant glioma who are receiving temozolomide will be accrued in this open label, phase 2, randomized single institution trial of aprepitant in combination with ondansetron versus ondansetron alone for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Sixty-eight (68) patients will be randomized to each arm of the study.
详细描述
Sixty-eight (68) patients will be randomized to each arm of the study. Patient randomization will be stratified by grade of tumor (1 or 2 versus 3 or 4) and the number of prior progressions (0 or 1 versus 2). Within each of the 4 strata defined by these factors, a permuted block randomization scheme will be used to assign patients to receive either aprepitant in combination with ondansetron or ondansetron alone.
Though the study is comparative, the goal of the study is to determine whether aprepitant is worthy of further investigation in this setting, and not to make definitive statements about the comparative effectiveness of ondansetron treatment with or without aprepitant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have histologically confirmed diagnosis of glioma (either low or high grade) and be either chemotherapy naïve or non-naïve and scheduled to receive temozolomide-based +/- Bevacizumab- based chemotherapy. Patients with recurrent disease whose diagnostic pathology confirmed glioma (either low or high grade) will not need re-biopsy.
- •Age ≥ 18 years
- •≤ 2 prior chemotherapeutic regimens
- •Patient is scheduled to receive temozolomide at either 150 mg/m2 or 200mg/m2 by mouth for 5 days out of a 28 day cycle +/- bevacizumab.
- •Study participation will occur during the first cycle of the 5 day temozolomide course.
- •An interval of at least 6 weeks between prior surgical resection and study enrollment
- •Karnofsky ≥ 60%.
- •Hematocrit > 29%, absolute neutrophil count (ANC) > 1,000 cells/µl, platelets > 100,000 cells/µl
- •Serum creatinine < 1.5 mg/dl, serum glutamic oxaloacetic transaminase (SGOT) and bilirubin < 1.5 times upper limit of normal
- •For patients on oral corticosteroids, they must be stable clinically on corticosteroids or tapered off prior to starting the study drug. For patients taking dexamethasone, the dose should not exceed 8 mg qd (or 4 mg twice a day), if clinically stable, and the dose should not be escalated over entry dose level, if clinically possible. The patient's dose of dexamethasone will be evaluated by the PI, the patient's study physician, and/or the study pharmacist on a case by case basis for safety. All doses of oral corticosteroids will be reduced by 50% to avoid drug to drug interactions with Aprepitant, unless oral corticosteroids are at physiologic dose (e.g. dexamethasone 1 mg, prednisone 10 mg, or cortisone 30 mg). It is recommended that oral corticosteroid doses be escalated back to full dose on Day 7 (2 days after Aprepitant is discontinued) based on Aprepitant half-life pharmacokinetic data, and expert clinical opinion.
- •Signed informed consent approved by the Institutional Review Board prior to patient entry
- •If sexually active, patients will take contraceptive measures for the duration of protocol treatment and continue until one month after treatment. The efficacy of hormonal contraceptives during and for 28 days following the last dose of Aprepitant may be reduced. Alternative or back-up methods of contraception must be used.
- •Approved rescue medication for the treatment of nausea and vomiting is permitted at the discretion of the investigator. The rescue antiemetics allowed will include: ondansetron, granisetron and lorazepam.
排除标准
- •Pregnant or breast-feeding (While both aprepitant and ondansetron are classified as Category B drugs, an eligibility criteria for this study is that the patient be scheduled to receive a temozolomide-based chemotherapy regimen +/- bevacizumab, which are Category D and C drugs respectively. Therefore, while not considered necessary for the administration of the current study drugs, a pregnancy test should be a part of normal clinical care for the patients in this study, if the patient is determined to be of child-bearing potential.)
- •No prior nitrosourea (e.g. lomustine, carmustine)
- •Inability or unwillingness to understand or cooperate with study procedures
- •Concurrent administration of CYP3A4 enzyme-inducing anti-epileptic drugs (EIAEDs) including phenytoin, phenobarbitol, carbamazepine, oxcarbazepine or primidone
- •Prohibited medications: Patients taking CYP3A4 enzyme inducers and moderate or strong inhibitors will be excluded from this trial.
- •Received any drug with potential anti-emetic effect within 24 hours prior to the start of study-designated chemotherapeutic agent: HT3 receptor or substance P/neurokinin 1(NK1) receptor antagonists; Dopamine receptor antagonists (metoclopramide); Phenothiazine anti-emetics (prochlorperazine, thiethylperazine and perphenazine); Diphenhydramine, scopolamine, chlorpheniramine maleate, trimethobenzamide; Haloperidol, droperidol, tetrahydrocannabinol, or nabilone
- •Any vomiting, retching or NCI Common Toxicity Criteria v.4.0 grade 2-4 nausea 24 hours preceding chemotherapy
- •Ongoing vomiting from any organic etiology
- •Will receive radiotherapy of cranium within one week prior to or during the study
研究组 & 干预措施
aprepitant+ondansetron
On day 1, patients will receive a single oral dose of Aprepitant 125 mg p.o, 1 hour before first dose of the 5-day oral temozolomide regimen. This will be followed by Aprepitant 80 mg p.o. on days 2 -5 (1 hour prior to temozolomide). Additionally, On days 1-5, patients receive a single dose of Ondansetron 30 minutes before the receiving their prescribed dose of 5-day oral temozolomide.
干预措施: aprepitant (Drug)
aprepitant+ondansetron
On day 1, patients will receive a single oral dose of Aprepitant 125 mg p.o, 1 hour before first dose of the 5-day oral temozolomide regimen. This will be followed by Aprepitant 80 mg p.o. on days 2 -5 (1 hour prior to temozolomide). Additionally, On days 1-5, patients receive a single dose of Ondansetron 30 minutes before the receiving their prescribed dose of 5-day oral temozolomide.
干预措施: ondansetron (Drug)
ondansetron
On days 1-5, patients receive a single dose of Ondansetron 30 minutes before the receiving their prescribed dose of 5-day oral temozolomide.
干预措施: ondansetron (Drug)
结局指标
主要结局
Proportion of Patients Achieving Complete Control (CC)
时间窗: 7 days
Complete control (CC): study days 1-7 (acute and delayed CINV) the proportion of patients achieving complete control (CC); defined as no emetic episode, no need for rescue medication during days 1-7; number of emetic episodes daily; time to first emetic episode; as captured by the MAT (MASCC Antiemesis Tool)/Osoba survey (MASCC refers to Multinational Association for Supportive Care in Cancer™). Severity of nausea and other toxicities measured daily by the NCI Common Toxicity Criteria (version 4.0).
次要结局
- Patient's Global Satisfaction With the Antiemetic Regimen(7 days)
- Proportion of Patients Achieving an Acute and Delayed Complete Response (CR)(7 days)
- Time to Treatment Failure(7 days)
研究者
Katy Peters
Assistant Professor
Duke University