A Standard Regimen of Dexamethasone in Comparison to Two Dex-sparing Regimens in Addition to NEPA in Preventing CINV in naïve NSCLC Patients to be Treated With Cisplatin Based Chemotherapy: a Three-arm, Open-label, Randomized Study
试验速览
- 阶段
- 3 期
- 入组人数
- 261
- 试验地点
- 26
- 主要终点
- Complete Response (CR)
研究概览
简要总结
This study evaluates the possibility to reduce the total dose of dexamethasone, when administered with NEPA, to prevent chemotherapy-induced nausea and vomiting (CINV) in Non-Small Cell Lung Cancer (NSCLC) patients receiving a cisplatin-based chemotherapy
详细描述
On day 1 (day of chemotherapy), all eligible patients will receive oral NEPA (300 mg netupitant/0.5 mg palonosetron), 60 minutes before chemotherapy, and intravenous dexamethasone 12 mg, 30 minutes before chemotherapy initiation.
For the prevention of delayed CINV, patients will be assigned randomly to one of the following treatment arms:
- Test arm A: no further anti-emetic prophylaxis on days 2 thorough 4;
- Test arm B: oral dexamethasone 4 mg once per day in the morning of days 2 and 3;
- Reference arm C: oral dexamethasone 4 mg twice per day on days 2 thorough 4.
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
- 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 ≥ 18 years old.
- •Histologically or cytologically confirmed diagnosis of NSCLC
- •Patients naїve to cisplatin-containing chemotherapy as well as any prior chemotherapy containing either highly or moderately emetogenic agents given for NSCLC or other malignancy.
- •Patients scheduled to receive their first cycle of cisplatin-based chemotherapy at a dose ≥70 mg/m2 either alone or in combination with other agents of low or minimal potential of emetogenicity (i.e., pemetrexed, gemcitabine±bevacizumab, vinorelbine) as neo-adjuvant, adjuvant or palliative therapy. Patients with progressive disease on therapy with an EGFR-TKI (Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors) and scheduled to receive cisplatin-based chemotherapy will be eligible for the study.
- •ECOG (Eastern Cooperative Oncology Group) Performance Status of 0-
- •Body Mass Index ≥18.
- •Written informed consent before study entry.
- •If women of childbearing potential age: effective contraceptive measures must be used during all the planned course of chemotherapy and up to 30 days after last NEPA administration.
- •Normal hepatic function (≤2 times the upper limit of normal for liver transaminases) and renal function (creatinine ≤ 1.5 times the upper limit of normal).
- •Ability and willingness of the patient to complete the diary and study questionnaires.
排除标准
- •Symptomatic brain metastases.
- •Patients scheduled to receive radiation therapy to the abdomen or pelvis within 1 week before day 1 or between day 1 and 5 following the first cycle of chemotherapy.
- •Patients scheduled to receive concurrent chemo/radiotherapy for NSCLC.
- •Treatment with investigational medications within 30 days before the study medication.
- •Myocardial infarction within the last 6 months.
- •Documented or known hypersensitivity to 5HT3RA (5-Hydroxytryptamine Receptor 3 Antagonists) or NK-1RA (Neurokinin-1 Receptor Antagonist) and excipients (see section 6.1 of Akynzeo SPC).
- •Uncontrolled diabetes mellitus or active infection.
- •Nausea and vomiting in the 24 hours before study treatment.
- •Chronic use of systemic corticosteroids (except for topical and inhaled corticosteroids) or any other agent with anti-emetic potential. Patients receiving dexamethasone on the day before chemotherapy for prevention of the pemetrexed-induced skin rash will be eligible for the study.
- •Patient's inability to take oral medication.
- •Gastrointestinal obstruction or active peptic ulcer.
- •Pregnancy or breast feeding.
- •Prior malignancies at other sites except surgically treated non-melanoma skin cancer, superficial cervical cancer, or other cancer from which the patient had been disease-free for at least 5 years (see also inclusion criteria if prior chemotherapy treatment).
- •Psychiatric or CNS (Central Nervous System) disorders interfering with ability to comply with study protocol.
研究组 & 干预措施
Arm A
Oral Netupitant/Palonosetron (NEPA) and intravenous Dexamethasone (DEX) on Day 1 of chemotherapy.
No further anti-emetic prophylaxis on days 2 thorough 4.
干预措施: Netupitant/Palonosetron (Drug)
Arm A
Oral Netupitant/Palonosetron (NEPA) and intravenous Dexamethasone (DEX) on Day 1 of chemotherapy.
No further anti-emetic prophylaxis on days 2 thorough 4.
干预措施: Dexamethasone (Drug)
Arm B
Oral Netupitant/Palonosetron (NEPA) and intravenous Dexamethasone (DEX) on Day 1 of chemotherapy.
Oral dexamethasone 4 mg once per day in the morning of days 2 and 3.
干预措施: Netupitant/Palonosetron (Drug)
Arm B
Oral Netupitant/Palonosetron (NEPA) and intravenous Dexamethasone (DEX) on Day 1 of chemotherapy.
Oral dexamethasone 4 mg once per day in the morning of days 2 and 3.
干预措施: Dexamethasone (Drug)
Arm C
Oral Netupitant/Palonosetron (NEPA) and intravenous Dexamethasone (DEX) on Day 1 of chemotherapy.
Oral dexamethasone 4 mg twice per day on days 2 thorough 4.
干预措施: Netupitant/Palonosetron (Drug)
Arm C
Oral Netupitant/Palonosetron (NEPA) and intravenous Dexamethasone (DEX) on Day 1 of chemotherapy.
Oral dexamethasone 4 mg twice per day on days 2 thorough 4.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Complete Response (CR)
时间窗: During the overall phase (day 1 thorough 5) of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days)
The proportion of patients achieving a complete response, defined as no emetic episode and no use of rescue medication, during the overall study period (day 1 thorough 5) of the first cycle of chemotherapy.
次要结局
- CR (acute and delayed).(During the acute (within 24 hours post-chemotherapy) and delayed (days 2 thorough 5) phases of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days))
- Complete control(During the acute (within 24 hours post-chemotherapy), delayed (days 2 thorough 5) and overall (days 1 thorough 5) phases of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days))
- Proportion of patients with no emetic episode(During the acute (within 24 hours post-chemotherapy), delayed (days 2 thorough 5) and overall (days 1 thorough 5) phases of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days))
- Patient global satisfaction with anti-emetic therapy,(On day 6 of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days))
- Cross-sectional baseline evaluation of weight loss (WL)(During the Screening phase (up to 7 days before the first cycle of chemotherapy administration - each cycle is 7 or 21 days))
- Nutritional intake(During the Screening phase (up to 7 days before the first cycle of chemotherapy administration - each cycle is 7 or 21 days))
- Proportion of patients with no nausea(During the acute (within 24 hours post-chemotherapy), delayed (days 2 thorough 5) and overall (days 1 thorough 5) phases of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days))
- Impact of nausea and vomiting on patient's quality of life(On day 6 of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days))
- Safety profile(During all the safety study period (up to three weeks after the start of cisplatin-based chemotherapy))
- Cancer-related symptom self-assessment(On day 1 of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days))
- Cancer-related symptom self-assessment association with WLGS and nutritional intake(On day 1 of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days))