A Pivotal Phase 3 Observer-Blind, Randomized Clinical Trial of the Efficacy and Safety of APF530 Compared to Aloxi For The Prevention of Acute-Onset and Delayed-Onset Chemotherapy-Induced Nausea and Vomiting Following The Administration of Either Moderately or Highly Emetogenic Chemotherapy Regimens
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,428
- 试验地点
- 52
- 主要终点
- Proportion of Patients With Complete Response (CR) During Acute Phase (0-24 Hours) After Administration of Chemotherapy Course 1
研究概览
简要总结
This randomized phase III trial is studying APF530 and dexamethasone to see how well they work compared with palonosetron and dexamethasone in preventing nausea and vomiting in patients receiving chemotherapy for cancer.
详细描述
OBJECTIVES:
Primary
- Compare the overall activity and effects of APF530 versus palonosetron hydrochloride in combination with dexamethasone for prophylaxis of acute- or delayed-onset, chemotherapy-induced nausea and vomiting in patients undergoing moderately or highly emetogenic chemotherapy for cancer.
Secondary
- Evaluate the safety, tolerability, and efficacy of APF530, in terms of prevention of acute- and delayed-onset nausea and vomiting, in these patients.
- Gather the pharmacokinetics of APF530 in a subset of patients during chemotherapy course 1.
- Gather ECG data (using 24-hour Holter monitoring) in a subset of patients during chemotherapy course 1.
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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically or cytologically confirmed malignant disease
- •No head and neck cancer or upper gastrointestinal cancer
- •Scheduled to receive a single day of moderately or highly emetogenic chemotherapy regimen (for ≤ 4 courses)
- •Chemotherapy administration ≤ 4 hours
- •Duration of each course ≤ 28 days
- •Causing nausea and vomiting in 30-100% of patients if untreated according to Hesketh algorithm
- •Must be able to receive standardized doses of dexamethasone for the prevention of emesis during study treatment
- •No greater than mild nausea or any vomiting within 24 hours before beginning study treatment
- •PATIENT CHARACTERISTICS:
- •ECOG performance status 0-2
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No known allergy or hypersensitivity to other selective 5-HT3 receptor antagonists or local anesthetics
- •QTc interval ≤ 500 ms
- •No cardiac abnormality predisposing the patient to arrhythmia
- •No psychological problem that, in the opinion of the investigator, is severe enough to preclude study participation
- •No recent history (i.e., ≤ 1 year) of alcohol or drug abuse
- •No concurrent condition that, in the opinion of the investigator, could affect assessment of study medication or interfere with the nausea/vomiting response (e.g., severe renal or hepatic impairment)
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •No radiotherapy 7 days prior to, during, and 5 days after completion of study treatment
- •More than 7 days since prior chemotherapy
- •More than 7 days since prior and no concurrent prohibited medications (e.g., CYP3A4 inhibitors or other antiemetic medications)
- •More than 7 days since prior antinausea medications
- •More than 30 days since prior treatment on an investigational trial
- •No other concurrent corticosteroids or dexamethasone at a different dose than study treatment
- •No concurrent use of APF530, palonosetron hydrochloride, or aprepitant as rescue medications
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive palonosetron hydrochloride IV, placebo subcutaneously (SC), and dexamethasone IV on day 1 of chemotherapy course 1. Patients in the high-risk (level 5) stratum also receive oral dexamethasone on days 2-4 of all treatment courses.
干预措施: dexamethasone (Drug)
Arm I
Patients receive palonosetron hydrochloride IV, placebo subcutaneously (SC), and dexamethasone IV on day 1 of chemotherapy course 1. Patients in the high-risk (level 5) stratum also receive oral dexamethasone on days 2-4 of all treatment courses.
干预措施: Palonosetron Hydrochloride (Drug)
Arm I
Patients receive palonosetron hydrochloride IV, placebo subcutaneously (SC), and dexamethasone IV on day 1 of chemotherapy course 1. Patients in the high-risk (level 5) stratum also receive oral dexamethasone on days 2-4 of all treatment courses.
干预措施: placebo (Other)
Arm II
Patients receive APF530 SC, placebo IV, and dexamethasone IV on day 1 of chemotherapy course 1. Patients then receive APF530 SC and dexamethasone IV on day 1 of chemotherapy courses 2-4. Patients in the high-risk (level 5) stratum also receive oral dexamethasone as in arm I.
干预措施: APF530 (Drug)
Arm II
Patients receive APF530 SC, placebo IV, and dexamethasone IV on day 1 of chemotherapy course 1. Patients then receive APF530 SC and dexamethasone IV on day 1 of chemotherapy courses 2-4. Patients in the high-risk (level 5) stratum also receive oral dexamethasone as in arm I.
干预措施: dexamethasone (Drug)
Arm II
Patients receive APF530 SC, placebo IV, and dexamethasone IV on day 1 of chemotherapy course 1. Patients then receive APF530 SC and dexamethasone IV on day 1 of chemotherapy courses 2-4. Patients in the high-risk (level 5) stratum also receive oral dexamethasone as in arm I.
干预措施: placebo (Other)
Arm III
Patients receive APF530 SC at a higher dose, placebo IV, and dexamethasone IV on day 1 of chemotherapy course 1. Patients then receive APF530 SC (at the same higher dose) and dexamethasone IV on day 1 of chemotherapy courses 2-4. Patients in the high-risk (level 5) stratum also receive oral dexamethasone as in arm I.
干预措施: APF530 (Drug)
Arm III
Patients receive APF530 SC at a higher dose, placebo IV, and dexamethasone IV on day 1 of chemotherapy course 1. Patients then receive APF530 SC (at the same higher dose) and dexamethasone IV on day 1 of chemotherapy courses 2-4. Patients in the high-risk (level 5) stratum also receive oral dexamethasone as in arm I.
干预措施: dexamethasone (Drug)
Arm III
Patients receive APF530 SC at a higher dose, placebo IV, and dexamethasone IV on day 1 of chemotherapy course 1. Patients then receive APF530 SC (at the same higher dose) and dexamethasone IV on day 1 of chemotherapy courses 2-4. Patients in the high-risk (level 5) stratum also receive oral dexamethasone as in arm I.
干预措施: placebo (Other)
结局指标
主要结局
Proportion of Patients With Complete Response (CR) During Acute Phase (0-24 Hours) After Administration of Chemotherapy Course 1
时间窗: 0-24 Hours
Complete Response is defined as no emetic episodes and no use of rescue medications
Proportion of Patients With CR During Delayed-onset Phase (24-120 Hours) After Administration of Chemotherapy Course 1
时间窗: 24-120 Hours
Complete Response is defined as no emetic episodes and no use of rescue medications
次要结局
- Proportion of Patients With Total Response During the Acute Phase, Delayed-onset Phase, and During Chemotherapy Course 1(0-120 Hours)
- Proportion of Patients With Complete Control During the Acute Phase (0-24 Hours), Delayed-onset Phase (24-120 Hours), and During Chemotherapy Course 1(0-120 Hours)
- Number of Emetic Episodes(Days 1-5)
- Time to First Treatment Failure(0-120 Hours)
- First and Overall Use of Rescue Medication(0-120 Hours)
- Severity of Nausea Daily and During Chemotherapy Course 1 (0-120 Hours)(0-120 Hours)
- Sustainability of Antiemetic Effect of APF530 Over Multiple Chemotherapy Courses(0-120 Hours)
- Quality of Life and the Impact of Nausea and Vomiting on Day 5(5 days)
- Patient's Global Satisfaction With Antiemetic Therapy During Acute Phase and Chemotherapy Course 1(0- 24 Hours)