Chemotherapy in KRAS Mutated Chemotherapy Naive Non-small Cell Lung Cancer Patients: a Phase III Study Comparing Cisplatin-pemetrexed With Carboplatin-paclitaxel-bevacizumab: NVALT 22
试验速览
- 阶段
- 3 期
- 入组人数
- 203
- 试验地点
- 28
- 主要终点
- progression free survival
研究概览
简要总结
The purpose of this study is to determine whether carboplatin-paclitaxel-bevacizumab results in a prolonged progression free survival compared to cisplatin-pemetrexed as first line treatment in patients with KRAS mutated non-small cell lung cancer.
详细描述
KRAS mutations occur in 30% of patients with non-small cell lung cancer, especially adenocarcinoma. For long time KRAS mutation has been related with poor prognosis and poor response to chemotherapy. Recent data however show that this is both not true. It seems that response, progression free survival and overall survival is similar in KRAS mutated. Until now no specific targeted therapy is available for KRAS mutated NSCLC patients. Optimization of treatment in advanced NSCLC patients with a KRAS mutation could also be achieved by selecting the best available chemotherapy treatment.
Two standard chemotherapy schemes are frequently used and FDA and EMA approved as first line treatment for patients with adenocarcinoma: cisplatin-pemetrexed and carboplatin-paclitaxel-bevacizumab.
The aim of this randomized phase III study is to compare two standard treatment regimens in patients with KRAS mutated, advanced stage NSCLC and the hypothesis is that bevacizumab with chemotherapy improves outcomes compared to chemotherapy alone as first line treatment. Furthermore the outcome for the different KRAS mutations will be studied.
Treatment with one of the two following chemotherapy combinations according to the label: carboplatin-paclitaxel-bevacizumab or cisplatin-pemetrexed q3wks for up to six cycles. Continuation maintenance with bevacizumab and pemetrexed is allowed until progression. Blood and archival tissue will be optionally collected for translational research. This may help to identify subgroups of patients who are likely better treated with a specific treatment regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •Histologically or cytologically confirmed (non-squamous) NSCLC incurable locally advanced or metastatic (stage IIIB and stage IV) disease.
- •Documented KRAS mutation
- •Chemotherapy-naive NSCLC patients. Adjuvant chemotherapy or chemoradiotherapy is allowed when given > 1 year for study entry. Previous anti-PD(L1) therapy for advanced disease is allowed.
- •At least one unidimensionally measurable lesion meeting RECIST1.
- •ECOG PS 0-2
- •Age ≥ 18 years
- •Adequate organ function, including:
- •Adequate bone marrow reserve: ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L.
- •Hepatic: bilirubin ≤1.5 x ULN, AP, ALT, AST ≤ 3.0 x ULN AP, ALT, and AST ≤5 xULN is acceptable if the liver has tumor involvement
- •Renal: calculated creatinine clearance ≥ 60 ml/min based on the Cockroft-Gault formula.
- •Urine protein (dip-stick) < 2 +; when ≥ 2 +: 24 hours urine protein ≤ 1 gr.
- •Signed informed consent
- •Male and female patients with reproductive potential must use an approved contraceptive method, if appropriate. Female patients with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
排除标准
- •Pregnant or lactating women
- •Clinically significant (i.e. active) cardiovascular disease: congestive heart failure >NYHA class 2; CVA or myocardial infarction < 6 months prior to study entry; uncontrolled hypertension (blood pressure systolic > 150 mmHg and/or diastolic > 100 mmHg)
- •History of hemoptysis ≥ grade 2 (bright red blood of at least 2,5 ml in the last 3 months)
- •Evidence of tumor invading major blood vessels on imaging (i.e. superior vena cava or pulmonary artery)
- •Patients with evidence or history of bleeding diathesis
- •Non-healing wound or ulcer
研究组 & 干预措施
carboplatin-paclitaxel- bevacizumab
carboplatin AUC 6, paclitaxel 200 mg/m2, bevacizumab 15 mg/kg all administered intravenously on day 1 every 3 weeks for 4-6 cycles, followed by bevacizumab maintenance every 3 weeks until progression
干预措施: carboplatin (Drug)
carboplatin-paclitaxel- bevacizumab
carboplatin AUC 6, paclitaxel 200 mg/m2, bevacizumab 15 mg/kg all administered intravenously on day 1 every 3 weeks for 4-6 cycles, followed by bevacizumab maintenance every 3 weeks until progression
干预措施: paclitaxel (Drug)
carboplatin-paclitaxel- bevacizumab
carboplatin AUC 6, paclitaxel 200 mg/m2, bevacizumab 15 mg/kg all administered intravenously on day 1 every 3 weeks for 4-6 cycles, followed by bevacizumab maintenance every 3 weeks until progression
干预措施: Bevacizumab (Drug)
cisplatin-pemetrexed
pemetrexed 500 mg/m2 administered intravenously on day 1 and cisplatin 75 mg/m2 administered intravenously on day 1 every 3 weeks for 4-6 cycles, followed by maintenance pemetrexed every 3 weeks until progression.
干预措施: Pemetrexed (Drug)
cisplatin-pemetrexed
pemetrexed 500 mg/m2 administered intravenously on day 1 and cisplatin 75 mg/m2 administered intravenously on day 1 every 3 weeks for 4-6 cycles, followed by maintenance pemetrexed every 3 weeks until progression.
干预措施: cisplatin (Drug)
结局指标
主要结局
progression free survival
时间窗: Every 6 weeks, from date of randomization until the date of progression of disease or of death from any cause, assessed up to 60 months
次要结局
- response by Crabb criteria (if applicable)(Every 6 weeks, from date of randomization until the date of progression of disease or of death from any cause, assessed up to 60 months)
- overall survival(date of randomization to the date of death from any cause, assessed up to 60 months.)
- outcome between G12V versus G12C versus other subtypes of KRAS mutations (mutational analysis on plasma and blood platelets).(date of randomization to the date of death from any cause, assessed up to 60 months.)
- disease control rate(Every 6 weeks, from date of randomization until the date of progression of disease or of death from any cause, assessed up to 60 months.)