A Phase II Study of L-BLP25 and Bevacizumab in Unresectable Stage IIIA and IIIB Non-Squamous Non-Small Cell Lung Cancer After Definitive Chemoradiation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 70
- 试验地点
- 88
- 主要终点
- Proportion of Patients With Target Adverse Events for the Step 2 Treatment
研究概览
简要总结
RATIONALE: Vaccines may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving vaccine therapy together with bevacizumab after chemotherapy and radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying the side effects of giving BLP25 liposome vaccine together with bevacizumab after chemotherapy and radiation therapy in treating patients with newly diagnosed stage IIIA or stage IIIB non-small cell lung cancer that cannot be removed by surgery.
详细描述
OBJECTIVES:
Primary
- To determine the safety of BLP25 liposome vaccine (tecemotide) and bevacizumab after definitive chemoradiotherapy and consolidation chemotherapy in patients with newly diagnosed, unresectable stage IIIA or IIIB nonsquamous cell non-small cell lung cancer.
Secondary
- To evaluate the overall survival and progression-free in patients treated with this regimen.
- To evaluate the toxicity of this regimen in these patients.
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
- •Histologically confirmed newly diagnosed nonsquamous non-small cell lung cancer (NSCLC), including the following subtypes:
- •Adenocarcinoma
- •Large cell undifferentiated
- •Bronchoalveolar cell
- •non-small cell carcinoma, not otherwise specified
- •Unresectable stage IIIA or stage IIIB disease
- •Patients with stage IIIA disease with mediastinal lymph node enlargement between 1 cm and 2.0 cm on computerized tomography (CT) scan must have these nodes biopsied (pathologic confirmation) to rule out resectability
- •Metastases to contralateral mediastinal or supraclavicular nodes allowed
- •Measurable or non-measurable disease, as defined by Response Evaluation Criteria in Solid Tumours (RECIST) criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •White blood cell (WBC) ≥ 4,000/mm³ OR Absolute neutrophil count (ANC) ≥ 2,000/mm³
- •Platelet count ≥ 140,000/mm³
- •Hemoglobin ≥ 9.0 g/dL
- •Total bilirubin ≤ 1.5 mg/dL
- •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)+ ≤ 2.5 times upper limit of normal
- •Serum creatinine ≤ 1.5 mg/mL OR creatinine clearance ≥ 45 mL/min
- •Urine protein:creatinine ratio < 1.0 by urine dipstick OR < 1 g of protein by 24-hour urine collection
- •INR ≤ 1.5 OR ≤ 3.0 if patient is on therapeutic anticoagulation
- •PTT normal
- •Fertile patients must use effective contraception before, during, and for ≥ 6 months after completion of bevacizumab
排除标准
- •Significant pleural effusion
- •CNS metastases by head CT scan or MRI within the past 4 weeks
- •Pregnant or breast-feeding
- •Prior chemotherapy or monoclonal antibodies for other cancers within 5 years prior to registration
- •Prior chemotherapy for lung cancer
- •Prior chest radiotherapy
- •Ongoing (lasting > 14 days) or active infection or ongoing (lasting > 14 days) fever within the past 6 months
- •Gross hemoptysis ≥ grade 2 (defined as ≥ ½ teaspoon of bright red blood per episode) within the past 3 months
- •Bleeding ≥ grade 2 or any bleeding requiring intervention
- •Clinically significant cardiovascular disease
- •Myocardial infarction within the past 6 months
- •New York Heart Association class III-IV congestive heart failure
- •Unstable angina pectoris
- •Serious cardiac arrhythmia requiring medication within the past 4 weeks
- •History of hypertensive crisis or hypertensive encephalopathy
- •Stroke or transient ischemic attack within the past 6 months
- •Peripheral vascular disease ≥ grade 2 within the past 6 months
- •Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
- •Psychiatric illness or social situation that would limit compliance with study requirements
- •History of uncontrolled hypertension (i.e., blood pressure ≥ 150/100 mm Hg) while on stable regimen of antihypertensive therapy
- •Significant traumatic injury or serious non-healing wound, ulcer, or bone fracture within the past 4 weeks
- •Concurrent major surgical procedure
- •Having anticipated major surgical procedure(s) during the course of the study
- •Concurrent daily aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory agents (NSAIDs) known to inhibit platelet function
- •Recognized immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia, or hereditary or congenital immunodeficiencies
- •Pre-existing medical condition requiring chronic steroids or immunosuppressive therapy
- •Autoimmune disease
- •Known hepatitis B or C
- •Immunotherapy (e.g., interferon, interleukin, sargramostim [GM-CSF], or filgrastim [G-CSF]) within 28 days prior to registration
- •Prior splenectomy
- •Hypersensitivity to any component of bevacizumab
- •Prior core biopsy or any other minor surgical procedure, excluding the placement of a vascular access device, within 7 days prior to registration
- •Step 2 Inclusion Criteria:
- •Serum creatinine ≤ 1.5 mg/ml or calculated creatinine clearance ≥ 45 ml/min
- •Urine dipstick must be ≤ 0-1+. If urine dipstick results > 1+, 24 hour urine for protein must be obtained. Patients must have < 1g protein/24 hours to participate in the study
- •Patient must be registered to step 2 within 28 days of completion of consolidation chemotherapy
- •Patient must have met all eligibility requirements for Step 1
- •Platelets ≥ 100,000/mm3
- •Step 2 Exclusion Criteria:
- •Progressive disease or unevaluable disease per RECIST criteria upon post- consolidation chemotherapy evaluation
- •Autoimmune disease
研究组 & 干预措施
Tecemotide/bevacizumab after chemoradiation
Concomitant Chemoradiotherapy: Patients (pts) receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 15-30 minutes weekly for 6 weeks. Pts also receive radiotherapy 5 days a week for 6½ weeks. Pts with CR, PR, or SD proceed to consolidation chemotherapy.
Consolidation chemotherapy: Pts receive paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression (PD) or unacceptable toxicity. Pts with CR, PR, or SD proceed to maintenance therapy.
Maintenance therapy: Pts receive a single dose of cyclophosphamide IV over 15-30 minutes 3 days before the first dose of bevacizumab and tecemotide. Pts then receive bevacizumab IV over 30-90 minutes on day 1 and tecemotide subcutaneously on days 1, 8, and 15 of courses 1 and 2 and on day 1 of every other course beginning in course 4. Treatment repeats every 21 days for up to 34 courses in the absence of PD or unacceptable toxicity.
干预措施: bevacizumab (Biological)
Tecemotide/bevacizumab after chemoradiation
Concomitant Chemoradiotherapy: Patients (pts) receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 15-30 minutes weekly for 6 weeks. Pts also receive radiotherapy 5 days a week for 6½ weeks. Pts with CR, PR, or SD proceed to consolidation chemotherapy.
Consolidation chemotherapy: Pts receive paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression (PD) or unacceptable toxicity. Pts with CR, PR, or SD proceed to maintenance therapy.
Maintenance therapy: Pts receive a single dose of cyclophosphamide IV over 15-30 minutes 3 days before the first dose of bevacizumab and tecemotide. Pts then receive bevacizumab IV over 30-90 minutes on day 1 and tecemotide subcutaneously on days 1, 8, and 15 of courses 1 and 2 and on day 1 of every other course beginning in course 4. Treatment repeats every 21 days for up to 34 courses in the absence of PD or unacceptable toxicity.
干预措施: Tecemotide (Biological)
Tecemotide/bevacizumab after chemoradiation
Concomitant Chemoradiotherapy: Patients (pts) receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 15-30 minutes weekly for 6 weeks. Pts also receive radiotherapy 5 days a week for 6½ weeks. Pts with CR, PR, or SD proceed to consolidation chemotherapy.
Consolidation chemotherapy: Pts receive paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression (PD) or unacceptable toxicity. Pts with CR, PR, or SD proceed to maintenance therapy.
Maintenance therapy: Pts receive a single dose of cyclophosphamide IV over 15-30 minutes 3 days before the first dose of bevacizumab and tecemotide. Pts then receive bevacizumab IV over 30-90 minutes on day 1 and tecemotide subcutaneously on days 1, 8, and 15 of courses 1 and 2 and on day 1 of every other course beginning in course 4. Treatment repeats every 21 days for up to 34 courses in the absence of PD or unacceptable toxicity.
干预措施: carboplatin (Drug)
Tecemotide/bevacizumab after chemoradiation
Concomitant Chemoradiotherapy: Patients (pts) receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 15-30 minutes weekly for 6 weeks. Pts also receive radiotherapy 5 days a week for 6½ weeks. Pts with CR, PR, or SD proceed to consolidation chemotherapy.
Consolidation chemotherapy: Pts receive paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression (PD) or unacceptable toxicity. Pts with CR, PR, or SD proceed to maintenance therapy.
Maintenance therapy: Pts receive a single dose of cyclophosphamide IV over 15-30 minutes 3 days before the first dose of bevacizumab and tecemotide. Pts then receive bevacizumab IV over 30-90 minutes on day 1 and tecemotide subcutaneously on days 1, 8, and 15 of courses 1 and 2 and on day 1 of every other course beginning in course 4. Treatment repeats every 21 days for up to 34 courses in the absence of PD or unacceptable toxicity.
干预措施: cyclophosphamide (Drug)
Tecemotide/bevacizumab after chemoradiation
Concomitant Chemoradiotherapy: Patients (pts) receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 15-30 minutes weekly for 6 weeks. Pts also receive radiotherapy 5 days a week for 6½ weeks. Pts with CR, PR, or SD proceed to consolidation chemotherapy.
Consolidation chemotherapy: Pts receive paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression (PD) or unacceptable toxicity. Pts with CR, PR, or SD proceed to maintenance therapy.
Maintenance therapy: Pts receive a single dose of cyclophosphamide IV over 15-30 minutes 3 days before the first dose of bevacizumab and tecemotide. Pts then receive bevacizumab IV over 30-90 minutes on day 1 and tecemotide subcutaneously on days 1, 8, and 15 of courses 1 and 2 and on day 1 of every other course beginning in course 4. Treatment repeats every 21 days for up to 34 courses in the absence of PD or unacceptable toxicity.
干预措施: paclitaxel (Drug)
Tecemotide/bevacizumab after chemoradiation
Concomitant Chemoradiotherapy: Patients (pts) receive paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 15-30 minutes weekly for 6 weeks. Pts also receive radiotherapy 5 days a week for 6½ weeks. Pts with CR, PR, or SD proceed to consolidation chemotherapy.
Consolidation chemotherapy: Pts receive paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression (PD) or unacceptable toxicity. Pts with CR, PR, or SD proceed to maintenance therapy.
Maintenance therapy: Pts receive a single dose of cyclophosphamide IV over 15-30 minutes 3 days before the first dose of bevacizumab and tecemotide. Pts then receive bevacizumab IV over 30-90 minutes on day 1 and tecemotide subcutaneously on days 1, 8, and 15 of courses 1 and 2 and on day 1 of every other course beginning in course 4. Treatment repeats every 21 days for up to 34 courses in the absence of PD or unacceptable toxicity.
干预措施: radiotherapy (Radiation)
结局指标
主要结局
Proportion of Patients With Target Adverse Events for the Step 2 Treatment
时间窗: Assessed every 3 weeks while on treatment and up to 5 years
The study is to evaluate the safety of the combination of tecemotide immunotherapy with bevacizumab. The target adverse events for the combined treatment are as follows: grade 4-5 hemorrhage, esophagitis, fistula, platelet count decrease (thrombocytopenia), encephalitis infection, or hepatic failure episodes.
次要结局
- Overall Survival(Every 3 months for patients < 2 years from study entry, and every 6 months if patient is 2-5 years from study entry; up to 5 years)
- Progression-free Survival(Every 3 months for patients < 2 years from study entry, and every 6 months if patient is 2-5 years from study entry; up to 5 years)