A Single-Arm, Phase 2 Trial of Pemetrexed, Cisplatin,and Bevacizumab as Induction, Followed by Pemetrexed and Bevacizumab as Maintenance, in First-Line Treatment of Nonsquamous Advanced NSCLC
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 109
- 试验地点
- 1
- 主要终点
- Progression-Free Survival
研究概览
简要总结
Participants with advanced non-small cell lung cancer (NSCLC) will receive a first-line treatment of Pemetrexed, Cisplatin and Bevacizumab as induction therapy followed by a maintenance treatment of Pemetrexed and Bevacizumab. Treatment will continue until disease progression or unacceptable toxicity occurs. The primary objective of this study is to measure how long this treatment could prevent the disease progression.
详细描述
The study will have 3 periods: a baseline period; a study treatment period, including both induction and maintenance treatment; and a follow-up period. Approximately 110 participants will be enrolled into the study, with the aim of having 100 evaluable participants. Eligible participants will first receive 4 cycles of induction chemotherapy with pemetrexed-cisplatin-bevacizumab. Participants who achieve a response or do not progress after completion of induction chemotherapy and have an adequate performance status will receive maintenance therapy with pemetrexed-bevacizumab. Treatment will continue until disease progression or unacceptable toxicity occurs. When treatment is discontinued, the participants health status will be monitored till death, loss to follow-up or data cut-off date.
Participants who continue to receive benefit from treatment at the time of data cut-off may receive continued access to pemetrexed and bevacizumab until disease progression, unacceptable toxicity, or any other reason at investigator or participants decision.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Histological or cytological diagnosis of nonsquamous Stage IIIB or Stage IV NSCLC that is not amenable to curative therapy
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •At least 1 unidimensionally measurable lesion meeting the Response Evaluation Criteria In Solid Tumors (RECIST) criteria
- •Adequate organ function, including the following:
- •Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥1.5 x 10^9 per Liter (10^9/L), platelets ≥100 x 10^9/L, and hemoglobin ≥10 gram per deciliter (g/dL)
- •Hepatic: bilirubin ≤1.5 times the upper limit of normal (ULN); alkaline phosphatase (AP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤3.0 x ULN (AP, AST, and ALT ≤5 x ULN is acceptable if liver has tumor involvement)
- •Renal: calculated creatinine clearance (CrCl) ≥45 milliliter per minute (mL/min) based on the original weight-based Cockcroft and Gault formula, and serum creatinine ≤1.5 x ULN
- •At the time of enrollment, if the urinalysis dipstick result is ≥2+ for protein, a 24-hour urine collection should be taken. In these cases, participants must have ≤1g protein/24 hours to be eligible for study participation
- •Participants must sign an Informed Consent Document (ICD)
排除标准
- •Have received prior systemic anticancer therapy for lung cancer (including adjuvant early-stage treatment for NSCLC)
- •Have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV
- •Have a second primary malignancy that is clinically detectable at the time of consideration for study enrollment
- •Have known central nervous system (CNS) disease, other than stable, treated brain metastasis. Stable, treated brain metastasis is defined as metastasis having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and post-treatment brain imaging (Computed Tomography [CT] scan or magnetic resonance imaging [MRI])
- •Are receiving concurrent administration of any other antitumor therapy
- •Have a history of gastrointestinal fistula, perforation, or abscess, inflammatory bowel disease, or diverticulitis
- •Have had significant weight loss (that is, ≥10%) over the previous 6 weeks before study entry
- •Have a history of gross hemoptysis (bright red blood of ≥½ teaspoon per episode of coughing) <3 months prior to enrollment or history or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding
- •Are taking or have recently taken (within 10 days of enrollment) full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes. Prophylactic use of anticoagulants is allowed; international normalized ratio (INR) should be <1.5 at study enrollment
- •Have a history of hypertension, unless hypertension is well controlled upon study entry (≤150/90 millimeter of mercury [mm Hg]) and the participant is on a stable regimen of antihypertensive therapy. Participants should not have any prior history of hypertensive crisis or hypertensive encephalopathy
- •Have had major surgery, open biopsy, or significant traumatic injury within 28 days prior to study enrollment, or anticipate the need for major surgical procedure during the course of the study
- •History of thrombotic disorders within the last 6 months prior to entry
研究组 & 干预措施
Study Treatment
干预措施: Pemetrexed (Drug)
Study Treatment
干预措施: Cisplatin (Drug)
Study Treatment
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Progression-Free Survival
时间窗: From enrollment to the first date of objectively determined Progressive Disease (PD) or death from any cause (every other cycle during study treatment and then every 6 weeks during follow-up period)(Baseline up to 36.1 Months)
Progression-Free Survival (PFS) is defined as the time from the date of study enrollment to the first date of objectively determined PD or death from any cause. PD is defined using Response Evaluation Criteria in Solid Tumours (RECIST) Guidelines (Version 1.0), as at least a 20% increase in the sum of longest diameter (LD) of target lesions, taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. For participants not known to have died as of the data cut-off date and who do not have objective PD, PFS will be censored at the date of the last objective progression-free disease assessment. For participants who receive subsequent systemic anticancer therapy, PFS will be censored at the date of the last objective progression-free disease assessment prior to post-discontinuation systemic therapy.
次要结局
- Overall Survival(From enrollment to the date of death from any cause (every cycle during study treatment, every 6 weeks during follow-up period until PD, and then at least every 3 Months) (Baseline up to 36.3 Months))
- Percentage of Participants With Confirmed Complete Response or Partial Response During Study Treatment (Induction and Maintenance)(From enrollment to objectively determined PD (assessment during study treatment completed at every other cycle till PD and at 30 day follow-up)(Baseline up to 104.1 Weeks))
- Percentage of Participants With Confirmed Response Complete or Partial Response During the Induction Treatment Only(From the time of study enrollment to the first date of objectively determined PD during the induction therapy (assessment during study treatment completed at every other cycle up to four cycles) (Baseline up to 4 cycles))
- Percentage of Participants With Confirmed Complete Response or Partial Response During the Maintenance Therapy Only(From the start of the maintenance to the first date of objectively determined PD during the maintenance therapy (assessment during maintenance treatment completed at every other cycle till PD and at 30 day follow-up)(Cycle 5 up to 104.1 Weeks))