Phase II Single Arm Trial of VEGF Trap in Patients With Recurrent Temozolomide-Resistant Malignant Gliomas
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 14
- 主要终点
- Progression-free Survival (PFS) at 6 Months
研究概览
简要总结
This phase II trial is studying how well VEGF Trap works in treating patients with recurrent malignant or anaplastic gliomas that did not respond to temozolomide. VEGF Trap may stop the growth of malignant or anaplastic gliomas by blocking blood flow to the tumor.
详细描述
PRIMARY OBJECTIVES:
I. Determine the therapeutic efficacy of VEGF Trap in patients with temozolomide-resistant malignant gliomas at first recurrence as measured by 6-month progression-free survival (PFS).
II. Determine the safety profile of VEGF Trap in these patients.
SECONDARY OBJECTIVES:
I. Determine the efficacy of this regimen as measured by radiographic response, PFS, time to progression, and overall survival.
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
- •International Normalized Ratio (INR) < = 1.5
- •Platelet count => 100,000/mm³
- •Hemoglobin => 10 g/dL (transfusion allowed)
- •Serum glutamic oxaloacetic transaminase (SGOT)/Serum glutamic pyruvic transaminase (SGPT) < = 2 times upper limit of normal (ULN)
- •Not pregnant or nursing
- •Negative pregnancy test
- •No previous Vascular endothelial growth factor (VEGF) Trap
- •At least 4 weeks since chemotherapy, surgery, or open biopsy
- •At least 2 weeks since vincristine
- •At least 6 weeks since carmustine, lomustine, fotemustine, or radiation therapy
- •At least 42 days since prior nitrosoureas
- •At least 3 weeks since procarbazine
- •No previous Gliadel wafers or bevacizumab
- •Tumor did not respond to previous radiation therapy and temozolomide
- •Karnofsky performance status (KPS) 60-100%
- •Life expectancy = > 8 weeks
- •White blood count (WBC) = >3,000/mm³
- •Absolute neutrophil count = > 1,500/mm³
- •Bilirubin < = 2 times ULN
- •Creatinine < = 1.5 mg/dL OR creatinine clearance= > 60 mL/min
- •Urine protein:creatinine ratio < = 1 OR 24-hour urine protein < = 500 mg/dL
- •Fertile patients must use effective contraception prior to, during, and for = > 6 months after completion of study treatment
- •No significant medical illnesses that, in the opinion of the investigator, cannot be adequately controlled with appropriate therapy or would preclude compliance with study treatment
- •No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- •No history of allergic reactions attributed to compounds of similar chemical or biological composition to other agents used in the study
- •No history of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off of all therapy for that disease for = >3 years
- •At least 7 days since prior noncytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin [radiosensitizer does not count])
- •At least 7 days since prior core biopsy
- •At least 28 days since prior investigational agents
- •No prior bevacizumab or vascular endothelial growth factor receptor inhibitors
- •No concurrent full-dose anticoagulants (e.g., warfarin or low molecular-weight heparin)
- •No clinically significant cardiovascular disease, including any of the following:
- •Cerebrovascular accident within the past 6 months
- •Uncontrolled hypertension, defined as blood pressure (BP) > 140/90 mm Hg or systolic BP > 180 mm Hg if diastolic BP < 90 mm Hg, on ≥ 2 repeated determinations on separate days within the past 3 months
- •Myocardial infarction, coronary artery bypass graft (CABG), or unstable angina pectoris within the past 6 months
- •New York Heart Association class III-IV congestive heart failure
- •No serious cardiac arrhythmia requiring medication
- •Clinically significant peripheral vascular disease within the past 6 months
- •Pulmonary embolism, deep vein thrombosis, or other thromboembolic event within the past 6 months
- •No evidence of bleeding diathesis or coagulopathy
- •No more than 1 prior chemotherapy regimen (initial treatment and treatment for 1 relapse)
- •Surgical resection for relapsed disease with no anticancer therapy instituted for up to 12 weeks followed by another surgical resection is considered 1 relapse
- •If prior therapy for a grade 3 glioma was given, surgical diagnosis of a high-grade glioma is considered the first relapse
- •Prior surgical, interstitial brachytherapy, or stereotactic radiosurgery not considered prior therapy
- •If prior therapy included interstitial brachytherapy or stereotactic radiosurgery, must have confirmation of true progressive disease rather than radiation necrosis based upon either positron emission tomography (PET) scan, thallium scanning, Magnetic Resonance (MR) spectroscopy, or surgical documentation of disease
- •Must show unequivocal radiographic evidence of tumor progression by MRI
- •Recent resection of recurrent or progressive tumor allowed
- •Residual disease not required
- •Temozolomide-resistant recurrent glioblastoma is defined as tumor progression or tumor recurrence during or after treatment with temozolomide-based chemotherapy regimens
- •Recovered from prior therapy
- 另有 24 项未显示
排除标准
- 未提供
结局指标
主要结局
Progression-free Survival (PFS) at 6 Months
时间窗: 6 months
This design yields 85% power to detect a true 30% 6-month PFS rate, while maintaining .91 probability of rejecting for a true 15% 6-month PFS rate. pts had MRIs at screening and at the 3rd and 5th cycles then every 8 weeks until progression. Response determined by modified MacDonald Criteria Complete Response (CR): Complete disappearance of all measurable and evaluable disease, no new lesions. no steroids Partial Response (PR): Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable lesions. no new lesions. steroid dose no \> than maximum dose used in first 8 weeks of treatment. Stable: Does not qualify for CR, PR, or progression steroid dose no \> than maximum dose used in first 8 weeks of treatment. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no increase) Clear clinical worsening.
Safety Profile - Toxicities
时间窗: Start to End of treatment 39 cycles or 1yr 7.5months (78 weeks)
number of cycles patient was able to have before developing a toxicity that required removing the patient from treatment. Treatment: Aflibercept 4mg/kg intravenously on day 1 of every 14-day cycle - 2 week cycle.
Safety Profile - Events That Discontinued Treatment
时间窗: Approximately 1 year (start of treatment - end of treatment)
number of patients who experienced toxicity that led to being taken off treatment
次要结局
- Response Rate Associated With VEGF Trap Therapy Defined as Proportions of Patients Experiencing Complete or Partial Response(Up to 2 years)
- Progression Free Survival (PFS) Rate for Subjects With Radiographic Response(up to 3 years)
- Overall Survival(3 years)