A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of Bavituximab Plus Docetaxel in patients with Previously Treated Locally Advanced or Metastatic Non-Squamous Non Small Cell Lung Cancer.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 120
- 试验地点
- 15
- 主要终点
- compare the objective response rate (ORR; complete response [CR] + partial response [PR]) of placebo plus docetaxel versus bavituximab plus docetaxel in patients with previously treated locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC).
研究概览
简要总结
This is a prospective, randomized, double-blind, placebo-controlled, multicenter, phase 2 study of a combination of bavituximab plus docetaxel in patients with previously treated locally advanced or metastatic non-squamous NSCLC. This study will be conducted in 2 periods: a Combination Therapy Period and a Monotherapy Period. This study will be conducted at 30 sites approx in US and India and up to 120 patients will be enrolled. The primary objective of this study is to compare the objective response rate (ORR; complete response [CR] + partial response [PR]) of placebo plus docetaxel versus bavituximab plus docetaxel in patients with previously treated locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC). Secondary objectives include comparing progression free survival (PFS), duration of response (DR), overall survival (OS), safety (type, frequency, severity and relationship of adverse events [AEs] to study drugs; laboratory and coagulation parameters; and human anti-chimeric antibodies [HACA]), and pharmacokinetic (PK) characteristics among the treatment arms. India, we are plan to enroll upto 60 patients and expecting the first patient to be in 30th of Jan 2011.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant and Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 60.00 Year(s)（—）
- 性别
- All
入选标准
- •Inclusion Criteria
- •Written informed consent has been obtained.
- •Adults over age 18 years of age with a life expectancy of at least 3 months.
- •Histologically or cytologically confirmed stage IIIB or stage IV non-squamous NSCLC who have progressed after 1 chemotherapy regimen (excluding docetaxel; paclitaxel is permitted).
- •Prior bevacizumab or targeted therapy is allowed.
- •Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST, Version 1.1) on cross-sectional imaging that is at least 2 cm in longest diameter (1 cm if measured by spiral computed tomography [CT]).
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤
- •Adequate hematologic function (absolute neutrophil count [ANC] ≥1,500 cells/μL; hemoglobin ≥9 g/dL, platelets ≥ 100,000/μL).
- •Adequate renal function (serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 60 mL/min).
- •Adequate hepatic function (bilirubin ≤ upper limit of normal [ULN], alanine aminotransferase [ALT] ≤ 1.5 x ULN and/or aspartate minotransferase [AST] ≤ 1.5 x ULN, alkaline phosphatase ≤ 2.5 x ULN).
- •ALT and/or AST and/or alk phos may be ≤ 5 × ULN if due to liver metastases.
- •Prothrombin time (PT) / international normalized ratio (INR) ≤ 1.5 x ULN.
- •Activated partial thromboplastin (aPTT) time ≤ 1.5 × ULN.
- •D-dimer ≤ 3 × ULN.
- •New York Heart Association classification I or II.
- •Female patients must have a negative urine or serum pregnancy test at screening (pregnancy test not required for patients with bilateral oophorectomy and/or hysterectomy or to those patients who are > 1 year postmenopausal).
- •All patients of reproductive potential must agree to use an approved form of contraception (as determined by the investigator).
排除标准
- •Exclusion criteria
- •Squamous, small cell, or mixed (eg, small cell and non-small cell) histology.
- •Known history of bleeding diathesis or coagulopathy (eg, von Willebrand disease or hemophilia).
- •Cavitary tumors or tumors invading or abutting large blood vessels.
- •Bleeding a) Clinically significant bleeding, such as gross hematuria, gastrointestinal bleeding, and hemoptysis within the 12 months before screening.
- •b) Minor hemoptysis associated with a procedure such as bronchoscopy is not exclusionary if resolved at least 3 months before screening.
- •Any history of thromboembolic events (eg, deep vein thrombosis or pulmonary thromboembolism); central venous catheter-related thrombosis 6 months prior is allowed.
- •Ongoing therapy with oral or parenteral anticoagulants; patients on low-dose anticoagulants to maintain patency of lines is eligible.
- •Concurrent hormone therapy (eg, estrogen contraceptives, hormone replacement, anti-estrogen).
- •Grade 2 or higher peripheral neuropathy (eg, numbness, tingling, and/or pain in distal extremities).
- •Radiotherapy within 2 weeks preceding Study Day
- •Major surgery within 4 weeks of Study Day
- •Pregnant or nursing women.
- •Uncontrolled intercurrent disease (e.g., diabetes, hypertension, thyroid disease).
- •Any history of symptomatic coronary artery disease, cerebrovascular accident, or transient ischemic attack.
- •A history of any condition requiring anti-platelet therapy (eg, phosphodiesterase inhibitors, adenosine diphosphate receptor antagonists), with the exception of general cardiovascular prophylaxis with aspirin ( 325 mg/day).
- •Serious non-healing wound (including wound healing by secondary intention, ulcer, or bone fracture).
- •Known chronic infection with human immunodeficiency virus (HIV) or viral hepatitis.
结局指标
主要结局
compare the objective response rate (ORR; complete response [CR] + partial response [PR]) of placebo plus docetaxel versus bavituximab plus docetaxel in patients with previously treated locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC).
时间窗: Objective Response Rate [ORR] is defined as the proportion of patients with confirmed CR or PR as a best response per the RECIST 1.1 criteria relative to all patients with baseline measurable disease. The ORR is monitored every 8-weeks for the duration the patient is active on study. Tumor assessments are performed at screening, cycle 3, cycle 5 and then every 8 weeks after cycle 5 until the patient discontinues the study.
次要结局
- comparing progression free survival (PFS), duration of response (DR), overall survival (OS), safety (type, frequency, severity and relationship of adverse events [AEs] to study drugs; laboratory and coagulation parameters; and human anti-chimeric antibodies [HACA)
- comparing progression free survival (PFS)(in each treatment arms)
- duration of response (DR), overall survival (OS)(Tumor assessments are performed at screening, cycle 3, cycle 5 and then every 8 weeks after cycle 5 until the patient discontinues the study)
- safety (type, frequency, severity and relationship of adverse events [AEs] to study drugs(in each treatment arms)
- laboratory and coagulation parameters(Laboratory parameters including coagulation tests are obtained at screening and day 1 of treatment cycles 1 through 6. Laboratory samples are immediately shipped to the central laboratory for analysis and the results, including coagulation results, are provided to the sites with 48-72hrs of the result being analyzed.)
- human anti-chimeric antibodies [HACA](HACA samples are collected at screening, Cycle 3 Day 1, Cycle 5 Day 1 and at Study Exit. HACA analysis will be performed at the end of the study and reported with the final clinical study report.)
- PK Samples(PK sampling is not being done in India. PK samples are being obtained from patients recruited in USA only.)