Dexamethasone-sparing Based on Netupitant/Palonosetron(NEPA) With Olanzapine for the Effect of Chemotherapy-induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy: a Randomized Noninferiority III Phase Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 644
- 试验地点
- 1
- 主要终点
- Percentage of patients with complete response (CR)
研究概览
简要总结
The objective of this Prospective, randomized, non inferiority phase III trial is to confirm the efficacy and saftey of dexamethasone-sparing combined with netupitant/palonostron and olanzapine for the prevention of chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy.
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
- 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
- •Male or female patients ≥18 years old
- •Patients who receive the high-emetic-risk anticancer agents.
- •Patients who do not take a medicine, for example, 5HT3 receptor antagonists, NK1 receptor antagonists, or research related agents, within 3 weeks prior to enrollment.
- •No nausea or vomiting (grade II or above) within 72 hours before the start of chemotherapy.
- •Subject has Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Subject has a life Expectation of at least 12 weeks.
- •In accordance with the indication of chemotherapy and basic requirements： Peripheral haematology: Hb ≥9.0g/dL; absolute neutrophil count ≥1.5×109/L; Platelet count ≥80×109/L Blood biochemistry: Total bilirubin < 1.25×ULN, ALT and AST ≤ 2.5×ULN; If liver metastasis, ALT and AST < 5×ULN, Creatinine ≤ 1×ULN, basic normal serum electrolyte (Na, Ka, Cl, Ca) Other important organs function normally.
- •Female patients of either non-childbearing potential or child-bearing potential use contraceptive methods throughout the clinical trial.
- •Female patients with child-bearing potential must is negative of pregnancy test.
- •Subjects voluntarily and strictly comply with the research protocol requirements and sign a written informed consent
- •Subjects can independently fill out patient diaries.
排除标准
- •Patients receiving moderate or high emetic radioation therapy within 1 week before chemotherapy or day 1 to 5 after chemotherapy.
- •Within 24 hours after chemotherapy, patients receiving any known or potential antiemetic agents and appearing symptoms vomiting, nausea, or mild nausea symptoms.
- •Scheduled to receive inducer or substrate or strong / moderate inhibitor of cytocrome P450 3A4 (CYP3A4) within 3 weeks prior to day
- •Patients who cannot tolerate chemotherapy drugs.
- •Serious cardiovascular, pulmonary disease, diabetes, mental and other diseases.
- •Pregnant , breastfeeding and woman with child-bearing potential who are unwilling or unable to take effective contraceptive measures.
- •Drug addict or alcohol abuse.
- •Hypocalcemia or any other condition that may cause vomiting.
- •Patients has significant factors that affect the absorption of oral medication, such as chronic diarrhea or obstruction.
- •Subjects has hypersensitivity to netupitant/palonostron capsules or any of its excipients.
- •Scheduled to receive any antiemetic agents within 3 weeks prior to day 1(including but not limited to: neurokin-1 (NK1) receptor antagonist, 5-HT3 receptor antagonists, olanzapine, scopolamine,et al.).
- •Scheduled to receive benzodiazepine, opioid or opioid derivatives (except midazolam, temazepam or triazolam)within 1 week before chemotherapy or day 1 to 5 after chemotherapy.
- •Subjects are currently enrolled in an other clinical study with any other clinical trials, investigational drugs or observational studies within 21 days of baseline.
- •Investigators judged other situations that may affect the progress and results of clinical research.
研究组 & 干预措施
HALF-DXMS GROUP
NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO)+ dexamethasone(6mg, day1, PO/IV)
干预措施: Dexamethasone Oral (Drug)
NEO-DXMS GROUP
NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO)+ dexamethasone(12mg, day1; 8mg day2-4, PO/IV).
干预措施: Dexamethasone Oral (Drug)
NEO-DXMS GROUP
NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO)+ dexamethasone(12mg, day1; 8mg day2-4, PO/IV).
干预措施: Netupitant / Palonosetron Oral Capsule [Akynzeo] (Drug)
HALF-DXMS GROUP
NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO)+ dexamethasone(6mg, day1, PO/IV)
干预措施: Netupitant / Palonosetron Oral Capsule [Akynzeo] (Drug)
NEO GROUP
NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO).
干预措施: Netupitant / Palonosetron Oral Capsule [Akynzeo] (Drug)
NEO GROUP
NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO).
干预措施: Olanzapine (Drug)
NEO-DXMS GROUP
NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO)+ dexamethasone(12mg, day1; 8mg day2-4, PO/IV).
干预措施: Olanzapine (Drug)
HALF-DXMS GROUP
NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO)+ dexamethasone(6mg, day1, PO/IV)
干预措施: Olanzapine (Drug)
结局指标
主要结局
Percentage of patients with complete response (CR)
时间窗: Within 0-120 hours from the initiation of chemotherapy
Percentage of patients with complete response (CR) defined defined as no vomiting with no use of rescue therapy
次要结局
- Percentage of Patients With CR (acute and delayed)(From the initiation of chemotherapy infusion(0h)up to beginning of day 6(-120 h))
- quality of life questionnaire(From initiation of chemotherapy to 168 hours after initiation of chemotherapy)
- Percentage of patients with overall total control (OTC)(During 0 ~ 24 hours and 0 ~ 168 hours post-chemotherapy)
- Percentage of patients with overall complete protection(OCP)(During the acute (within 24 hours post-chemotherapy) and delayed (days 2 thorough 5) phases of chemotherapy)
- incidence of adverse events(From initiation of chemotherapy to 168 hours after initiation of chemotherapy)
研究者
Jian Zhang,MD
Director of Phase I Clinical Trial Department; Professor, Chief physician of oncology department
Fudan University