Phase II Randomized, Open-Label Study of Cetuximab and Bevacizumab in Combination With Paclitaxel and Carboplatin in Patients With Stage IIIB/IV Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 121
- 试验地点
- 1
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
The primary objective of this study will be to determine the progression free survival of patients with stage IIIb/IV non-small cell lung cancer (NSCLC) treated with dual agent monoclonal antibody therapy consisting of cetuximab and bevacizumab in combination with two different regimens of paclitaxel and carboplatin chemotherapy.
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
- •The patient has histologically or cytologically confirmed non-small cell lung cancer (NSCLC), except squamous cell carcinoma. Mixed tumors will be categorized by the predominant cell type, but the presence of small cell lung cancer elements will make the patient ineligible. Cytologic or histologic elements can be established on metastatic tumor aspirates or biopsy.
- •The patient has advanced NSCLC (Stage IIIB with malignant pleural effusion or Stage IV or recurrent disease).
- •Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
- •The patient's Eastern Cooperative Oncology Group (ECOG) performance status is 0 or
- •The patient has adequate hematologic function as defined by an Absolute Neutrophil Count greater than or equal to 1500/mm³,hemoglobin greater than or equal to 9 gm/dL, and a platelet count greater than or equal to 100,000/mm³ obtained within 2 weeks prior to the first dose of study medication.
- •The patient has adequate hepatic function as defined by a total bilirubin greater than or equal to 1.5 mg/dL and transaminases and alkaline phosphatase less than or equal to 5 x the Upper Limit of Normal (ULN) obtained within 2 weeks prior to the first dose of study medication.
- •The patient has adequate renal function as defined by serum creatinine less than or equal to 1.5 x ULN or calculated creatinine clearance (CrCl) >60 mL/minute, and urine dipstick for proteinuria <1+ (ie, either 0 or trace) obtained within 2 weeks prior to the first dose of study medication. If urine dipstick is greater than or equal to 1+, then a 24-hour urine for protein must demonstrate <500 mg of protein in 24 hours to allow participation in the study.
- •The patient has adequate coagulation function as defined by International Normalized Ratio less than or equal to 1.5 and a Prothrombin time and partial thromboplastin time less than or equal to ULN obtained within 2 weeks prior to the first dose of study medication.
- •The patient, if a woman of childbearing potential, agrees to use an accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the study. If a male and sexually active, the patient agrees to use effective contraception.
排除标准
- •The patient has known Central Nervous System metastases. A head computed tomography (CT) is required within 4 weeks prior to the first dose of study medication (magnetic resonance imagines [MRIs] are also acceptable).
- •The patient has received prior cetuximab therapy.
- •The patient has received prior bevacizumab therapy.
- •The patient has received prior systemic chemotherapy or radiation therapy at any time for lung cancer.
- •Any concurrent malignancy other than basal cell skin cancer, or carcinoma in situ of the cervix. Patients with adequately treated cancers of other histologies who have been disease-free for more than 3 years prior to the first treatment dose are eligible.
- •Concurrent treatment with other anti-cancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemoembolization, or targeted therapy.
- •The patient has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •The patient has a history of thrombotic or hemorrhagic disorders.
- •The patient has uncontrolled hypertension (>150/100 mmHg) on a standard regimen of anti-hypertensive therapy.
- •The patient is receiving chronic daily treatment with aspirin (>325 mg/day) or nonsteroidal anti-inflammatory agents known to inhibit platelet function.
- •The patient is receiving treatment with dipyridamole (Persantine®), ticlopidine (Ticlid®), clopidogrel (Plavix®) and /or cilostazol (Pletal®).
- •The patient is receiving anti-coagulation therapy. Prophylactic anti-coagulation of venous access devices is allowed. Caution should be taken on treating patients with low dose heparin or low molecular weight heparin for deep vein thrombosis (DVT) prophylaxis during treatment with bevacizumab as there may be an increased risk of bleeding.
- •Patients with a history of gross hemoptysis (defined as bright red blood or greater than or equal to ½ teaspoon).
- •The patient has a serious non-healing wound ulcer, bone fracture, or major surgical procedure within 30 days prior to first dose of study medication.
- •Elective or planned major surgery to be performed during the course of the trial.
- •The patient has a pre-existing neuropathy >grade
- •The patient, if a woman, is pregnant or lactating.
研究组 & 干预措施
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/6)
Cycles 1-6:
- Cetuximab 400 mg/m² initial dose on day 1 and then 250 mg/m² given every week
- Bevacizumab 15 mg/kg given on day 8 of every 3 week cycle
- Paclitaxel 200 mg/m² on day 1 of every 3 week cycle
- Carboplatin area under curve (AUC=6 min*mg/mL) on day 1 of every 3 week cycle
Patients who demonstrate a response or stable disease after six cycles of therapy may continue on weekly cetuximab monotherapy until disease progression, unacceptable toxicity, or another withdrawal criterion is met
干预措施: Cetuximab (Biological)
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/6)
Cycles 1-6:
- Cetuximab 400 mg/m² initial dose on day 1 and then 250 mg/m² given every week
- Bevacizumab 15 mg/kg given on day 8 of every 3 week cycle
- Paclitaxel 200 mg/m² on day 1 of every 3 week cycle
- Carboplatin area under curve (AUC=6 min*mg/mL) on day 1 of every 3 week cycle
Patients who demonstrate a response or stable disease after six cycles of therapy may continue on weekly cetuximab monotherapy until disease progression, unacceptable toxicity, or another withdrawal criterion is met
干预措施: Bevacizumab (Biological)
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/6)
Cycles 1-6:
- Cetuximab 400 mg/m² initial dose on day 1 and then 250 mg/m² given every week
- Bevacizumab 15 mg/kg given on day 8 of every 3 week cycle
- Paclitaxel 200 mg/m² on day 1 of every 3 week cycle
- Carboplatin area under curve (AUC=6 min*mg/mL) on day 1 of every 3 week cycle
Patients who demonstrate a response or stable disease after six cycles of therapy may continue on weekly cetuximab monotherapy until disease progression, unacceptable toxicity, or another withdrawal criterion is met
干预措施: Paclitaxel (Drug)
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/6)
Cycles 1-6:
- Cetuximab 400 mg/m² initial dose on day 1 and then 250 mg/m² given every week
- Bevacizumab 15 mg/kg given on day 8 of every 3 week cycle
- Paclitaxel 200 mg/m² on day 1 of every 3 week cycle
- Carboplatin area under curve (AUC=6 min*mg/mL) on day 1 of every 3 week cycle
Patients who demonstrate a response or stable disease after six cycles of therapy may continue on weekly cetuximab monotherapy until disease progression, unacceptable toxicity, or another withdrawal criterion is met
干预措施: Carboplatin (Drug)
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/3)
Cycles 1-6:
- Cetuximab 400 mg/m² initial dose on day 1 and then 250 mg/m² given every week
- Bevacizumab 15 mg/kg given on day 8 of every 3 week cycle
Cycles 1-3:
- Paclitaxel 200 mg/m² on day 1 of each 3 week cycle for the first 3 cycles
- Carboplatin AUC=6 min*mg/mL on day 1 of each 3 week cycle for the first 3 cycles
Patients who demonstrate a response or stable disease after six cycles of therapy may continue on weekly cetuximab monotherapy until disease progression, unacceptable toxicity, or another withdrawal criterion is met
干预措施: Cetuximab (Biological)
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/3)
Cycles 1-6:
- Cetuximab 400 mg/m² initial dose on day 1 and then 250 mg/m² given every week
- Bevacizumab 15 mg/kg given on day 8 of every 3 week cycle
Cycles 1-3:
- Paclitaxel 200 mg/m² on day 1 of each 3 week cycle for the first 3 cycles
- Carboplatin AUC=6 min*mg/mL on day 1 of each 3 week cycle for the first 3 cycles
Patients who demonstrate a response or stable disease after six cycles of therapy may continue on weekly cetuximab monotherapy until disease progression, unacceptable toxicity, or another withdrawal criterion is met
干预措施: Bevacizumab (Biological)
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/3)
Cycles 1-6:
- Cetuximab 400 mg/m² initial dose on day 1 and then 250 mg/m² given every week
- Bevacizumab 15 mg/kg given on day 8 of every 3 week cycle
Cycles 1-3:
- Paclitaxel 200 mg/m² on day 1 of each 3 week cycle for the first 3 cycles
- Carboplatin AUC=6 min*mg/mL on day 1 of each 3 week cycle for the first 3 cycles
Patients who demonstrate a response or stable disease after six cycles of therapy may continue on weekly cetuximab monotherapy until disease progression, unacceptable toxicity, or another withdrawal criterion is met
干预措施: Paclitaxel (Drug)
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/3)
Cycles 1-6:
- Cetuximab 400 mg/m² initial dose on day 1 and then 250 mg/m² given every week
- Bevacizumab 15 mg/kg given on day 8 of every 3 week cycle
Cycles 1-3:
- Paclitaxel 200 mg/m² on day 1 of each 3 week cycle for the first 3 cycles
- Carboplatin AUC=6 min*mg/mL on day 1 of each 3 week cycle for the first 3 cycles
Patients who demonstrate a response or stable disease after six cycles of therapy may continue on weekly cetuximab monotherapy until disease progression, unacceptable toxicity, or another withdrawal criterion is met
干预措施: Carboplatin (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Randomization to PD or date of death from any cause up to 33.1 months
PFS is defined as the time from randomization until the date of progression of disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD ≥20% increase in sum of longest diameter of target lesions. Participants who are alive and without PD will be censored at the date of their last tumor assessment.
次要结局
- Overall Survival(Randomization to the date of death from any cause up to 42.7 months)
- Percentage of Participants Achieving an Objective Overall Response (Overall Response Rate)(Randomization to measured progressive disease up to 31.8 months)
- Duration of Overall Response(Time of first response to the first date of PD or death due to any cause up to 31.8 months)
- Percentage of Participants With Symptomatic Response (Symptom Response Rate)(From date of partial response until progression of disease up to 31.8 months)