Olanzapine With or Without Fosaprepitant for the Prevention of Chemotherapy Induced Nausea and Vomiting (CINV)in Patients Receiving Highly Emetogenic Chemotherapy (HEC): A Phase III Randomized, Double Blind, Placebo-Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 690
- 试验地点
- 565
- 主要终点
- No Nausea Rate Defined as a Response of 0 in the Nausea Item of Nausea and Vomiting Daily Diary/Questionnaire in the Overall (0-120 Hours), Acute (0-24 Hours), and Delayed (24-120 Hours) Periods
研究概览
简要总结
This randomized phase III trial studies how well olanzapine with or without fosaprepitant work in preventing chemotherapy induced nausea and vomiting in cancer patients receiving chemotherapy that causes vomiting. Olanzapine and fosaprepitant dimeglumine may help control nausea and vomiting in patients during chemotherapy. Olanzapine is usually given in combination with other drugs, including fosaprepitant dimeglumine. It is not yet known if olanzapine when given with other drugs, is still effective without using fosaprepitant dimeglumine for controlling nausea and vomiting.
详细描述
PRIMARY OBJECTIVES:
I. To compare between the two study arms the proportion of patients with no nausea for the overall (0-120 hours post-chemotherapy), acute (0-24 hours post-chemotherapy), and delayed periods (24-120 hours post-chemotherapy) for patients receiving highly emetogenic chemotherapy (HEC).
SECONDARY OBJECTIVES:
I. To compare between the two study arms the complete response (CR) rates (no emetic episodes and no use of rescue medication) in the acute, delayed, and overall periods.
II. To compare between the two study arms, the incidences of potential toxicities that have been ascribed to olanzapine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Investigator)
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
- •Diagnosis of malignant disease of any stage; (stage I through stage IV)
- •No prior history of chemotherapy for any malignancy
- •Scheduled to receive intravenous HEC (highly emetogenic chemotherapy) (either cisplatin-containing regimen or doxorubicin and cyclophosphamide [AC]); cisplatin, given on a single day, at a dose of >= 70 mg/m^2, with or without other chemotherapy agent(s) OR doxorubicin (60 mg/m^2) plus cyclophosphamide (600 mg/m^2)
- •No nausea or vomiting =< 24 hours prior to registration
- •Negative pregnancy test (serum or urine) done =< 7 days prior to registration, for women of childbearing potential only
- •* A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
- •No known diagnosis of dementia; patients with stable treated brain metastases are eligible to participate
- •No known history of central nervous system (CNS) disease (e.g. seizure disorder)
- •No treatment with another antipsychotic agent such as olanzapine, risperidone, quetiapine, clozapine, phenothiazine or butyrophenone =< 30 days prior to registration
- •No chronic phenothiazine administration as an antipsychotic agent (patients may receive prochlorperazine and other phenothiazines as rescue anti-emetic therapy but not within 24 hours prior to registration)
- •No use of amifostine within 7 days prior to registration
- •No radiotherapy within 7 days prior to registration or planned for one week after the current dose of chemotherapy
- •No use of quinolone antibiotic therapy within 7 days prior to registration
- •No chronic alcoholism (as determined by the investigator)
- •No known hypersensitivity to olanzapine
- •No known uncontrolled cardiac arrhythmia, no known uncontrolled congestive heart failure, or no acute myocardial infarction within the previous six months
- •No history of uncontrolled diabetes mellitus, i.e., no diabetic ketoacidosis; within 6 months prior to registration; patients are eligible if they have controlled diabetes on diet, oral agents, and/or insulin
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
- •Patients must be able to read and comprehend English; local translation, including verbal translation of patient-reported outcomes (PROs) is not permitted
- •Serum creatinine =< 2.0 mg/dL =< 120 days prior to registration
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) =< 120 days prior to registration
排除标准
- 未提供
研究组 & 干预措施
Arm I (fosaprepitant dimeglumine, olanzapine)
Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, fosaprepitant dimeglumine IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Palonosetron Hydrochloride (Drug)
Arm I (fosaprepitant dimeglumine, olanzapine)
Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, fosaprepitant dimeglumine IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Ondansetron Hydrochloride (Drug)
Arm I (fosaprepitant dimeglumine, olanzapine)
Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, fosaprepitant dimeglumine IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Dexamethasone (Drug)
Arm I (fosaprepitant dimeglumine, olanzapine)
Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, fosaprepitant dimeglumine IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Fosaprepitant Dimeglumine (Drug)
Arm I (fosaprepitant dimeglumine, olanzapine)
Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, fosaprepitant dimeglumine IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Olanzapine (Drug)
Arm II (placebo, olanzapine)
Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, placebo IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment (with no placebo) may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Palonosetron Hydrochloride (Drug)
Arm II (placebo, olanzapine)
Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, placebo IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment (with no placebo) may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Ondansetron Hydrochloride (Drug)
Arm II (placebo, olanzapine)
Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, placebo IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment (with no placebo) may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Dexamethasone (Drug)
Arm II (placebo, olanzapine)
Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, placebo IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment (with no placebo) may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Olanzapine (Drug)
Arm II (placebo, olanzapine)
Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, placebo IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment (with no placebo) may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Placebo (Other)
结局指标
主要结局
No Nausea Rate Defined as a Response of 0 in the Nausea Item of Nausea and Vomiting Daily Diary/Questionnaire in the Overall (0-120 Hours), Acute (0-24 Hours), and Delayed (24-120 Hours) Periods
时间窗: Up to 120 hours
The specific measure will be based on the proportion of patients with a value of 0, as measured by the single nausea item (scale 0-10, 0 is no symptoms, 10 is worst symptoms) of the Questionnaire. A modified intent-to-treat principle will be applied for statistical analysis of efficacy in evaluable patients. The proportions of patients with no nausea during the overall, the acute, and the delayed period will be summarized by treatment arm. They will be tested in a sequential manner, using a Simes gatekeeping procedure to maintain the overall significance level at the specified by the Lan-DeMets family of alpha spending function. The difference in no nausea proportions between arms will be estimated along with a one-sided 95% confidence interval. The tests and the confidence intervals will be constructed using normal approximation of the binomial distribution adjusted for the non-inferiority margin.
次要结局
- Potential Toxicities as Ascribed to Olanzapine as Measured by the Nausea and Vomiting Daily Diary/Questionnaire(Up to 120 hours)
- Total Frequency of Rescue Medication as Measured by the Nausea and Vomiting Daily Diary/Questionnaire(Over 5 Days per each of the 4 cycles)
- Complete Response (CR) (no Emetic Episodes and no Use of Rescue Medication) During the Acute, Delayed and the Overall Periods as Measured by the Nausea and Vomiting Daily Diary/Questionnaire(Up to 120 hours)
- Average Nausea Scores (0-10) Repeatedly Measured by the Nausea and Vomiting Daily Diary/Questionnaire(Up to 1 year)