Phase I Trial of R115777 With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Antitumor activity
研究概览
简要总结
This phase I trial is studying the side effects and best dose of tipifarnib when given together with temozolomide and radiation therapy in treating patients with newly diagnosed glioblastoma multiforme or gliosarcoma. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy, such as temozolomide, 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 damage tumor cells. Combining tipifarnib, temozolomide, and radiation therapy may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. Establish MTD for R115777 in combination with Temozolomide with radiation in patients not on EIAEDs.
II. To define the safety of R115777 in combination with Temozolomide with radiation in this patient population.
III. To assess for evidence of antitumor activity in this patient population.
OUTLINE: This is a multicenter, dose-escalation study of tipifarnib. Patients are stratified according to concurrent use of enzyme-inducing antiepileptic drugs (yes [closed to accrual as of 3/15/05] vs no).
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
- •Patients will have histologically proven intracranial Glioblastoma Multiforme (GBM) or gliosarcoma (GS)
- •Diagnosis will have been established by biopsy or resection within 4 weeks prior to registration
- •Patients must not have received previous radiotherapy to the brain
- •Patients must not have received cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy directed against the brain tumor; patients who received Gliadel wafers will be excluded; patients may have received or be receiving corticosteroids, non-EIAEDs, analgesics, and other drugs to treat symptoms or prevent complications
- •Cranial MRI or contrast CT must have been performed within 21days of study entry; the use of MRI rather than CT is preferred; the same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement; if the surgical procedure was a resection, cranial MRI or contrast CT performed with 96 hours of resection is preferred but not required; patients without measurable or assessable disease are eligible
- •Patients must have a plan to begin partial brain radiotherapy within 5-9 days after beginning R115777, and within 35 days (5 weeks) of the surgical procedure that established the diagnosis; radiotherapy must be given at the Radiation Oncology Department of the registering ABTC institution; radiotherapy must be given by external beam to a partial brain field in daily fractions of 2.0 Gy, to a planned total dose to the tumor of 60.0 Gy; stereotactic radiosurgery and brachytherapy will not be allowed
- •Patients must be willing to forego other drug therapy against the tumor while being treated with R115777 and temozolomide
- •All patients must sign an informed consent indicating that they are aware of the investigational nature of this study; patients must sign an authorization for the release of their protected health information; patients must be registered with the Adult Brain Tumor Consortium Central Office (ABTC CO) prior to treatment with study drug
- •Life expectancy > 8 weeks
- •Patients must have a Karnofsky performance status of >= 60
- •Patients must have adequate bone marrow function and the test must be performed within 14 days prior to registration; eligibility level for hemoglobin may be reached by transfusion
- •WBC >= 3,000/µl
- •ANC >= 1,500/mm^3
- •Platelet count of >= 100,000/mm^3
- •Hemoglobin >= 10 gm/dl
- •Patients must have adequate liver function and the test must be performed within 14 days prior to registration
- •SGOT < 2 times ULN
- •Bilirubin < 2 times ULN
- •Patients must have adequate renal function before starting therapy and the test must be performed within 14 days prior to registration
- •Creatinine < 1.5 mg/dL
- •Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy; patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism
- •Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible
- •This study was designed to include women and minorities, but was not designed to measure differences of intervention effects; males and females will be recruited with no preference to gender; no exclusion to this study will be based on race; minorities will actively be recruited to participate
- •Patients must not have active infection
- •Women must not be pregnant or Breast-feeding, and women with reproductive potential must practice adequate contraception; the anti-proliferative effects of the investigational agent may be detrimental to the developing fetus or nursing infant
- •Patients must not be on chronic coumadin therapy for prior medical problems (e.g. cardiac valve prophylaxis); this is due to a presumed interaction with coumadin and ZARNESTRA leading to a significant increase in INR; patients who develop or have recently developed a deep venous thrombosis or pulmonary embolism who are on or will take coumadin will be allowed to participate; however, the investigator should be prepared to monitor patients INR closely
排除标准
- 未提供
研究组 & 干预措施
Treatment (tipifarnib, temozolomide, radiation therapy)
See Detailed Description
干预措施: tipifarnib (Drug)
Treatment (tipifarnib, temozolomide, radiation therapy)
See Detailed Description
干预措施: temozolomide (Drug)
Treatment (tipifarnib, temozolomide, radiation therapy)
See Detailed Description
干预措施: radiation therapy (Radiation)
结局指标
主要结局
Antitumor activity
时间窗: Up to 5 years
MTD of tipifarnib
时间窗: Week 10
Safety variables will be summarized by descriptive statistics. Adverse events that occur will be reported for each dose level and described in terms of incidence and severity. Laboratory data will be presented by dose level at each observation time. Values outside of normal limits will be identified and their frequency calculated. Parameters will be described based on the CTCAE severity grading. Distribution by CTCAE severity grade (when applicable) and clinical relevance will be given.
Incidence of adverse events
时间窗: Up to 5 years
Safety variables will be summarized by descriptive statistics. Adverse events that occur will be reported for each dose level and described in terms of incidence and severity. Laboratory data will be presented by dose level at each observation time. Values outside of normal limits will be identified and their frequency calculated. Parameters will be described based on the CTCAE severity grading. Distribution by CTCAE severity grade (when applicable) and clinical relevance will be given.
次要结局
未报告次要终点