A Phase III Multicenter, Randomized, Double-blind, Double-dummy, Active-controlled, Parallel Group Study of the Efficacy and Safety of Oral Netupitant Administered in Combination With Palonosetron and Dexamethasone Compared to Oral Palonosetron and Dexamethasone for the Prevention of Nausea and Vomiting in Cancer Patients Receiving Moderately Emetogenic Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,455
- 试验地点
- 171
- 主要终点
- Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, at Cycle 1
研究概览
简要总结
NETU-08-18 is a two-arm clinical study assessing efficacy and safety of a single oral dose of netupitant and palonosetron, two antiemetic drugs, versus oral palonosetron, both given with oral dexamethasone. The objective of the study is to demonstrate that netupitant and palonosetron are more effective than palonosetron alone, to prevent nausea and vomiting induced by moderately emetogenic cancer chemotherapy after administration of repeated cycles of chemotherapy.
详细描述
NETU-08-18 is a two-arm clinical study assessing efficacy and safety of a single oral dose of netupitant and palonosetron, two antiemetic drugs, versus oral palonosetron, both given with oral dexamethasone. Study is organised in two phases: cycle-1 and a multi-cycle extension. Safety assessment is performed separately in cycle 1 (arm 1 and arm 2) and in multi-cycle extension (arm 3 and arm 4).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy will be permitted.
- •Scheduled to receive first course of an anthracycline and cyclophosphamide containing moderately emetogenic chemotherapy (MEC) regimen for the treatment of a solid malignant tumor: cyclophosphamide I.V. (500 to 1500 mg/m2) and I.V. doxorubicin (more or equal to 40 mg/m2) or cyclophosphamide I.V. (500 to 1500 mg/m2) and I.V. epirubicin (more or equal to 60 mg/m2).
- •If scheduled to receive chemotherapy agents of minimal to low emetogenic potential they could be given on any day.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or
- •Female patients of either non-childbearing potential or child-bearing potential with a commitment to use contraceptive methods throughout the clinical trial
- •Hematologic and metabolic status adequate for receiving a moderately emetogenic regimen based on laboratory criteria (Total Neutrophils,Platelets, Bilirubin, Liver enzymes, Serum Creatinine or Creatinine Clearance)
- •The following inclusion criteria must be checked prior inclusion at each cycle of the Multiple-Cycle Extension:
- •Participation in the study during the next cycle of chemotherapy is considered appropriate by the investigator Satisfactory study compliance in the preceding cycle of chemotherapy and related study procedures.
- •Scheduled to receive the same chemotherapy regimen as cycle 1
- •Adequate hematologic and metabolic status as defined for cycle 1
排除标准
- •If female, pregnant or lactating.
- •Current use of illicit drugs or current evidence of alcohol abuse.
- •Scheduled to receive any highly emetogenic chemotherapy (HEC) from Day 1 to Day 5 or moderately emetogenic chemotherapy (MEC) from Day 2 to Day 5 following the allowed MEC regimen.
- •Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to Day 1 or between Days 1 to 5 in cycle
- •Any vomiting, retching, or mild nausea within 24 hours prior to Day
- •Symptomatic primary or metastatic central nervous system (CNS) malignancy.
- •Active peptic ulcer disease, gastrointestinal obstruction, increased intracranial pressure, hypercalcemia, an active infection or any uncontrolled medical condition (other than malignancy) that, in the opinion of the investigator, may confound the results of the study, represent another potential etiology for emesis and nausea (other than chemotherapy-induced nausea and vomiting, CINV) or pose unwarranted risks in administering the study drugs to the patient.
- •Known hypersensitivity or contraindication to 5-HT3 receptor antagonists or dexamethasone.
- •Previously received a neurokin-1 (NK1) receptor antagonist
- •Participation in a clinical trial involving oral netupitant administered in combination with palonosetron.
- •Any investigational drugs taken within 4 weeks prior to Day 1 of cycle 1, and/or is scheduled to receive any investigational drug during the study.
- •Systemic corticosteroid therapy at any dose within 72 hours prior to Day 1 of cycle
- •Scheduled to receive bone marrow transplantation and/or stem cell rescue therapy.
- •Any medication with known or potential antiemetic activity within 24 hours prior to Day 1 of cycle 1
- •Scheduled to receive any strong or moderate inhibitor of cytocrome P450 3A4 (CYP3A4) or its intake within 1 week prior to Day
- •Scheduled to receive any of the following CYP3A4 substrates: terfenadine, cisapride, astemizole, pimozide.
- •Scheduled to receive any CYP3A4 inducer or its intake within 4 weeks prior to Day
- •History or predisposition to cardiac conduction abnormalities, except for incomplete right bundle branch block.
- •History of risk factors for Torsade de Point (heart failure, hypokalemia, family history of Long QT Syndrome).
- •Severe cardiovascular diseases, including myocardial infarction within 3 months prior to Day 1, unstable angina pectoris, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic Congestive Heart Failure (CHF) New York Heart Association (NYHA) class III-IV, and severe uncontrolled arterial hypertension.
- •Any illness or condition that, in the opinion of the investigator, may confound the results of the study or pose unwarranted risks in administering the investigational product to the patient.
- •Concurrent medical condition that would preclude administration of dexamethasone such as systemic fungal infection or uncontrolled diabetes.
- •The following exclusion criteria must be checked prior inclusion at each cycle of the Multiple-Cycle Extension:
- •If female, pregnant or lactating
- •Active infection or uncontrolled disease except for malignancy.
- •Started any of the restricted medications.
- •Any vomiting, retching, or mild nausea within 24 hours prior to Day 1.
研究组 & 干预措施
Palonosetron+dexamethasone-cycle 1
Oral palonosetron 0.50 mg (Aloxi) with oral dexamethasone (20 mg) both given on Day 1, prior to each scheduled chemotherapy cycle
干预措施: Dexamethasone (Drug)
Netupitant and Palonosetron+dexamethasone-cycle 1
Oral netupitant/palonosetron (300 mg/0.50 mg) hard capsule with oral dexamethasone (12 mg), both given on Day 1, prior to each scheduled chemotherapy cycle
干预措施: Netupitant and Palonosetron (Drug)
Netupitant and Palonosetron+dexamethasone-cycle 1
Oral netupitant/palonosetron (300 mg/0.50 mg) hard capsule with oral dexamethasone (12 mg), both given on Day 1, prior to each scheduled chemotherapy cycle
干预措施: Dexamethasone (Drug)
Palonosetron+dexamethasone-cycle 1
Oral palonosetron 0.50 mg (Aloxi) with oral dexamethasone (20 mg) both given on Day 1, prior to each scheduled chemotherapy cycle
干预措施: Palonosetron (Drug)
Netupitant and Palonosetron+dexamethasone-multicycle extension
Oral netupitant/palonosetron (300 mg/0.50 mg) hard capsule with oral dexamethasone (12 mg), both given on Day 1, prior to each scheduled chemotherapy cycle
干预措施: Netupitant and Palonosetron (Drug)
Netupitant and Palonosetron+dexamethasone-multicycle extension
Oral netupitant/palonosetron (300 mg/0.50 mg) hard capsule with oral dexamethasone (12 mg), both given on Day 1, prior to each scheduled chemotherapy cycle
干预措施: Dexamethasone (Drug)
Palonosetron+dexamethasone-multicycle extension
Oral palonosetron 0.50 mg (Aloxi) with oral dexamethasone (20 mg) both given on Day 1, prior to each scheduled chemotherapy cycle
干预措施: Palonosetron (Drug)
Palonosetron+dexamethasone-multicycle extension
Oral palonosetron 0.50 mg (Aloxi) with oral dexamethasone (20 mg) both given on Day 1, prior to each scheduled chemotherapy cycle
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, at Cycle 1
时间窗: 25-120 hours
次要结局
- Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication at Cycle 1(0-24 hours)
- Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, at Cycle 1(0-120 hours)