Phase I/II Study to Evaluate the Efficacy and Safety of Combination Chemotherapy With Carboplatin, Bortezomib and Bevacizumab as First Line Therapy in Patients With Advanced Non-small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Number of Subjects Who Require Dose Delay/Reduction in Dose of Bortezomibin the First Cycle
研究概览
简要总结
A pilot trial of combination of bortezomib, bevacizumab and carboplatin as first line therapy in patients with metastatic Non-Small Cell Lung Cancer (NSCLC). Phase I and II study of this combination in first line setting will be conducted in order to properly estimate the efficacy and safety of this regimen. This will form the basis for future studies comparing this combination to what is now considered standard regimen for first line therapy in patients with NSCLC, carboplatin, paclitaxel and bevacizumab.
详细描述
Study design and methodology The study will have two phases.
The phase I will use traditional dose escalation model (3-6 patient per dose level) to determine the maximum tolerated dose (MTD).
*[In phase II, either level III or (MTD) will be used in the same every 21 day cycle to evaluate the efficacy and safety of the regimen in first line treatment of advanced NSCLC]* not conducted.
Treatments administered
In phase I, three dose levels of weekly bortezomib will be studied in conjunction with fixed dose carboplatin and bevacizumab on a 21 day cycle to define the maximum tolerated dose (MTD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 SCLC (adeno- and large cell, anaplastic carcinoma and broncho-alveolar-carcinoma). Patients with squamous-cell histology are eligible with extra thoracic or peripheral lung lesions only.
- •Sputum cytology alone not acceptable evidence of cell type. Cytologic specimens obtained by brushing, washings, or needle aspiration of defined lesions will be acceptable. Mixed tumors will be categorized by the predominant cell type unless a small cell anaplastic elements are present, in which case the patient is ineligible.
- •Stage III B because of pleural effusion or Stage IV disease
- •Measurable disease.
- •Age: 18 years or older
- •No history of thrombotic, hemorrhagic, or coagulopathy disorders
- •international normalized ratio (INR<1.5) and a prothrombin time (PTT) no greater than normal limits of normal within 1 week prior to registration. NB: subjects with lung cancer placed on anticoagulant therapy for a thrombotic event are not eligible for this study.
- •No gross hemoptysis (defined as bright red blood of ½ teaspoon or more)
- •No central nervous system (CNS) or brain metastasis
- •Laboratory Criteria (completed <2 weeks before enrollment):
- •Hematologic: white blood cell (WBC) > 3500/mm3 or absolute neutrophil count (ANC) > 1500/mm3 and platelet count > 100 000/ mm3;
- •Hepatic: Total bilirubin < 1.5 mg/dl
- •Renal: Creatinine < 1.5 mg/dl. or calculated
- •Creatinine clearance > 45 ml/min (NB: Urine protein:creatinine ratio in exclusion criteria)
- •Eastern Cooperative Oncology Group (ECOG) performance status < 2
- •Be free of active infection.
- •Be available for active follow up.
- •No prior chemotherapy for metastatic disease.
- •Be disease free for > 5 years if they had a prior second malignancy other than treated basal cell carcinoma or squamous cell skin cancer, or carcinoma in situ of the cervix.
- •Female subject post-menopausal; surgically sterilized or willing to use an acceptable method of birth control for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study.
排除标准
- •CNS or brain metastasis
- •Patient has = or greater Grade 2 peripheral neuropathy within 14 days before enrollment.
- •Known previous sensitivity reactions with boron, or mannitol,
- •Patients with known HIV positivity
- •Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
- •Blood pressure of >150/100 mmHG
- •History of myocardial infarction or stroke within 6 months
- •Clinically significant peripheral vascular disease
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study.
- •Minor surgical procedure such as fine needle aspirations or core biopsies within 7 days prior to day 0
- •Urine protein: Creatinine ratio > 1.0 at screening
- •History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to Day 0
- •Serious, non-healing wound, ulcer, or bone fracture
- •Lung carcinoma or any histology in close proximity to a major vessel or cavitation
- •Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- •Patient has received other investigational drugs with 14 days before enrollment or is expected to participate in an experiment drug study during this study treatment.
- •Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
研究组 & 干预措施
Bortezomib 1.3 mg/m2
Level 1 of Bortezomib Dose Escalation in combination with Carboplatin AUC6, Bevacizumab 15 mg/kg and Taxotere 70 + G-CSF
干预措施: Bortezomib 1.3 mg/m2 (Drug)
Bortezomib 1.3 mg/m2
Level 1 of Bortezomib Dose Escalation in combination with Carboplatin AUC6, Bevacizumab 15 mg/kg and Taxotere 70 + G-CSF
干预措施: Carboplatin AUC 6 (Drug)
Bortezomib 1.3 mg/m2
Level 1 of Bortezomib Dose Escalation in combination with Carboplatin AUC6, Bevacizumab 15 mg/kg and Taxotere 70 + G-CSF
干预措施: Bevacizumab (Drug)
Bortezomib 1.3 mg/m2
Level 1 of Bortezomib Dose Escalation in combination with Carboplatin AUC6, Bevacizumab 15 mg/kg and Taxotere 70 + G-CSF
干预措施: Taxotere (Drug)
Bortezomib 1.6 mg/m2
Level 2 of Bortezomib Dose Escalation in combination with Carboplatin AUC6, Bevacizumab 15 mg/kg and Taxotere 70 + G-CSF
干预措施: Bortezomib 1.6 mg/m2 (Drug)
Bortezomib 1.6 mg/m2
Level 2 of Bortezomib Dose Escalation in combination with Carboplatin AUC6, Bevacizumab 15 mg/kg and Taxotere 70 + G-CSF
干预措施: Carboplatin AUC 6 (Drug)
Bortezomib 1.6 mg/m2
Level 2 of Bortezomib Dose Escalation in combination with Carboplatin AUC6, Bevacizumab 15 mg/kg and Taxotere 70 + G-CSF
干预措施: Bevacizumab (Drug)
Bortezomib 1.6 mg/m2
Level 2 of Bortezomib Dose Escalation in combination with Carboplatin AUC6, Bevacizumab 15 mg/kg and Taxotere 70 + G-CSF
干预措施: Taxotere (Drug)
Bortezomib 1.8 mg/m2
Level 3 of Bortezomib Dose Escalation in combination with Carboplatin AUC6, Bevacizumab 15 mg/kg and Taxotere 70 + G-CSF
干预措施: Bortezomib 1.8 mg/m2 (Drug)
Bortezomib 1.8 mg/m2
Level 3 of Bortezomib Dose Escalation in combination with Carboplatin AUC6, Bevacizumab 15 mg/kg and Taxotere 70 + G-CSF
干预措施: Carboplatin AUC 6 (Drug)
Bortezomib 1.8 mg/m2
Level 3 of Bortezomib Dose Escalation in combination with Carboplatin AUC6, Bevacizumab 15 mg/kg and Taxotere 70 + G-CSF
干预措施: Bevacizumab (Drug)
Bortezomib 1.8 mg/m2
Level 3 of Bortezomib Dose Escalation in combination with Carboplatin AUC6, Bevacizumab 15 mg/kg and Taxotere 70 + G-CSF
干预措施: Taxotere (Drug)
结局指标
主要结局
Number of Subjects Who Require Dose Delay/Reduction in Dose of Bortezomibin the First Cycle
时间窗: up to 21 days for each dosing cycle
Dose limiting toxicity at Level 1,2 and 3: Number of subjects who required dose delay/reduction in dose of bortezomib in the first cycle of treatment. DLT defined by any of the following during first cycle: (1) GR4 neutropenia or thrombocytopenia, (2) Greater than GR3 non-hematological toxicity except alopecia or inadequately treated nausea or vomiting or (3) neurosensory toxicity of GR2 with pain or any neurotoxicity greater than GR2.
次要结局
未报告次要终点
研究者
William Walsh
Study Principle Investigator
University of Massachusetts, Worcester