A Study of Pemetrexed Plus Carboplatin Followed by Maintenance Pemetrexed vs Paclitaxel Plus Carboplatin and Bevacizumab Followed by Maintenance Bevacizumab in Patients With Advanced NCSLC of Nonsquamous Histology
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 361
- 试验地点
- 1
- 主要终点
- Progression Free Survival Without Grade 4 Toxicity (G4PFS) as Measured by the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
研究概览
简要总结
The purpose of this study is to compare the regimens of pemetrexed, carboplatin with pemetrexed maintenance and paclitaxel, carboplatin, bevacizumab with bevacizumab maintenance in participants with Stage IV nonsquamous non-small cell lung cancer.
详细描述
This is a multicenter, randomized, open-label, Phase III trial. Eligible participants will be randomized in a 1:1 ratio to receive pemetrexed and carboplatin followed by pemetrexed or paclitaxel, carboplatin, and bevacizumab followed by bevacizumab as their study treatment. Participants randomized to Pemetrexed + Carboplatin + Pemetrexed will receive folic acid, vitamin B12, and dexamethasone as stated in the pemetrexed label. Before administration of paclitaxel, participants randomized to Paclitaxel + Carboplatin + Bevacizumab will receive premedication (dexamethasone, diphenhydramine, and cimetidine or ranitidine) as recommended in the paclitaxel label.
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
- •a histologic or cytologic diagnosis of advanced non-small cell lung cancer (NSCLC) [Stage IV from the American Joint Committee on Cancer Staging Criteria (AJCC) staging system, version 7.0, including both M1a and M1b], other than predominantly squamous cell histology, that is not amenable to curative therapy. Participants may not have received any prior systemic chemotherapy, immunotherapy, targeted therapy, or biological therapy, including adjuvant therapy, for any stage of NSCLC.
- •prior radiation therapy is allowed to < 25% of the bone marrow; however, prior radiation to the whole pelvis not allowed.
- •good performance status.
- •adequate organ function.
- •estimated life expectancy of at least 12 weeks.
排除标准
- •known central nervous system (CNS) disease, other than treated brain metastasis.
- •major surgical procedure, open biopsy, open pleurodesis, or significant traumatic injury within 28 days prior to study or have an anticipated need for major surgery during the study.
- •core biopsy or other minor surgical procedure, excluding placement of vascular access device, closed pleurodesis, thoracentesis, and mediastinoscopy, within 7 days prior to study.
- •history of gastrointestinal fistula, perforation, or abscess, inflammatory bowel disease, or diverticulitis.
- •currently receiving ongoing treatment with full-dose warfarin or equivalent
- •significant vascular disease within 6 months prior to Day 1 of Cycle
- •evidence of bleeding diathesis or coagulopathy.
- •serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the participant's ability to adhere to the protocol.
- •serious cardiac condition, such as myocardial infarction, angina, or heart disease.
- •inadequately controlled hypertension.
- •any prior history of hypertensive crisis or hypertensive encephalopathy.
- •serious, nonhealing wound, active ulcer, or untreated bone fracture.
- •another active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within the last 5 years.
- •previously received treatment with paclitaxel, carboplatin, pemetrexed, or bevacizumab (prior intravitreal administration of bevacizumab does not preclude study participation).
- •pregnant or breast-feeding.
- •history of stroke or transient ischemic attack within 6 months prior to study.
- •known sensitivity to any component of paclitaxel, carboplatin, pemetrexed, or bevacizumab.
- •history of hemoptysis within 3 months prior to randomization.
- •unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs).
- •unwilling to take folic acid or vitamin B12 supplementation.
- •clinically significant third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage. Participants with M1a disease with pleural effusions are eligible if the effusions can be adequately controlled.
研究组 & 干预措施
Paclitaxel + Carboplatin + Bevacizumab
Paclitaxel, Carboplatin, and Bevacizumab followed by Bevacizumab
干预措施: Bevacizumab (Biological)
Pemetrexed + Carboplatin + Pemetrexed
Pemetrexed and Carboplatin followed by Pemetrexed
干预措施: Pemetrexed (Drug)
Pemetrexed + Carboplatin + Pemetrexed
Pemetrexed and Carboplatin followed by Pemetrexed
干预措施: Carboplatin (Drug)
Paclitaxel + Carboplatin + Bevacizumab
Paclitaxel, Carboplatin, and Bevacizumab followed by Bevacizumab
干预措施: Carboplatin (Drug)
Paclitaxel + Carboplatin + Bevacizumab
Paclitaxel, Carboplatin, and Bevacizumab followed by Bevacizumab
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Progression Free Survival Without Grade 4 Toxicity (G4PFS) as Measured by the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
时间窗: Randomization to measured progressive disease or treatment discontinuation up to 39.49 months
G4PFS was defined as the duration from the date of randomization to the earliest occurrence date of one of the following three events: Common Terminology Criteria (CTC) grade 4 adverse events (G4AEs), or progressive disease (PD) or death from any cause, whichever occurred earlier. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. For participants who had no G4AEs, or PD, or death at the time of the data inclusion cutoff, PFS was censored at their last objective progression-free disease assessment prior to the cutoff date or the date of initiation of subsequent systemic anticancer therapy.
次要结局
- Overall Survival (OS)(Randomization to date of death from any cause up to 39.49 months)
- Progression Free Survival (PFS)(Randomization to measured progressive disease up to 39.49 months)
- Percentage of Participants With Complete Response or Partial Response (Overall Tumor Response Rate)(Baseline to date of objective progressive disease up to 39.49 months)
- Disease Control Rates Defined as Complete Response (CR), Partial Response (PR), and Stable Disease (SD)(Baseline to date of objective progressive disease up to 39.49 months)