A Phase I/II Trial of OSI-774 in Patients With Recurrent Malignant Gliomas and Malignant Gliomas Post Radiation Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 136
- 试验地点
- 7
- 主要终点
- Define Maximum Tolerated Dose (MTD) of Erlotinib by Phase 1 Cohorts
研究概览
简要总结
Phase I/II trial to study the effectiveness of erlotinib in treating patients who have recurrent malignant glioma or recurrent or progressive meningioma. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.
详细描述
OBJECTIVES:
Phase 1 I. Determine the maximum tolerated dose of erlotinib in patients with recurrent malignant glioma or recurrent or progressive meningioma.
II. Determine the safety profile of this drug in these patients. III. Determine the pharmacokinetics of this drug in these patients.
Phase 2 I. Determine the 6-month progression-free survival (recurrent malignant glioma) II.12-month survival of patients treated with this drug (stable glioblastoma post radiation therapy)
Phase 2 - Secondary Recurrent Malignant Glioma I. Objective Tumor Response rate associated with erlotinib therapy in recurrent or progressive malignant glioma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •One of the following diagnoses:
- •Histologically confirmed intracranial malignant glioma
- •Glioblastoma multiforme (GBM), anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed oligoastrocytoma, or malignant astrocytoma not otherwise specified
- •Original histology of low-grade glioma allowed provided a subsequent histology of malignant glioma is confirmed
- •Histologically or radiographically confirmed recurrent or progressive benign or malignant meningioma
- •Progressive disease or tumor recurrence on MRI or CT scan
- •Phase I: No more than 3 prior relapses and no more than 2 prior chemotherapy* or biologic therapy regimens
- •Phase II: No more than 2 prior relapses and no more than 2 prior chemotherapy* or biologic therapy regimens
- •Patients with progressive disease must have failed prior radiotherapy* that was completed at least 4 weeks ago
- •Patients with progressive disease between 4 and 12 weeks after completion of external beam radiotherapy must have clear evidence of progression on MRI
- •Patients with GBM who have completed external beam radiotherapy and do not show progression are eligible
- •Patients with progressive disease after interstitial brachytherapy or stereotactic radiosurgery must have confirmed true progression rather than radiation necrosis based upon positron-emission tomography, thallium scanning, MRI, or surgical documentation
- •Measurable or evaluable disease
- •Performance status - Karnofsky 60-100%
- •More than 8 weeks
- •WBC at least 3,000/mm^3
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Hemoglobin at least 10 mg/dL (transfusion allowed)
- •Bilirubin less than 1.5 times upper limit of normal (ULN)
- •SGOT less than 1.5 times ULN
- •Creatinine less than 1.5 mg/dL
- •None of the following ophthalmic abnormalities:
- •Abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)
- •Congenital abnormality (e.g., Fuch's dystrophy)
- •Abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
- •Abnormal corneal sensitivity test (Schirmer test or similar tear production test)
- •Patients found to have dry eyes on examination but have an otherwise normal examination allowed
- •No active infection
- •No other serious concurrent medical illness
- •No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
- •No other disease that would obscure toxicity or dangerously alter drug metabolism
- •No significant medical illness that would preclude study participation
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective barrier contraception during and for 12 weeks after study participation
- •See Disease Characteristics
- •At least 1 week since prior thalidomide
- •At least 1 week since prior interferon
- •At least 4 weeks since prior SU5416 or other experimental biologic agents
- •See Disease Characteristics
- •No prior chemotherapy (including polifeprosan 20 with carmustine implant [Gliadel wafers]) for patients with stable GBM
- •At least 2 weeks since prior vincristine
- •At least 3 weeks since prior procarbazine
- •At least 6 weeks since prior nitrosoureas
- •At least 1 week since prior tamoxifen
- •See Disease Characteristics
- •Recovered from prior radiotherapy
- •No more than 6 weeks since prior external beam radiotherapy for patients with GBM without evidence of progression
- •Recovered from prior surgery
- 另有 6 项未显示
排除标准
- 未提供
研究组 & 干预措施
Phase 1 Dose Escalation
Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
erlotinib hydrochloride given orally
Other: pharmacological study.
干预措施: erlotinib hydrochloride (Drug)
Phase 1 Dose Escalation
Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
erlotinib hydrochloride given orally
Other: pharmacological study.
干预措施: pharmacological study (Other)
Phase 2 recurrent malignant gliomas and nonprogressive GBM
Phase II: Patients not concurrently receiving EIAEDs are treated with erlotinib as above at a predetermined dose (150mg/day.
patients requiring surgery treated 7 days prior to tumor removal (150mg/day)
PK analysis and effects of erlotinib on epidermal growth factor receptor (EGFR)
erlotinib hydrochloride given orally
Other: pharmacological study, laboratory biomarker analysis.
干预措施: erlotinib hydrochloride (Drug)
Phase 2 recurrent malignant gliomas and nonprogressive GBM
Phase II: Patients not concurrently receiving EIAEDs are treated with erlotinib as above at a predetermined dose (150mg/day.
patients requiring surgery treated 7 days prior to tumor removal (150mg/day)
PK analysis and effects of erlotinib on epidermal growth factor receptor (EGFR)
erlotinib hydrochloride given orally
Other: pharmacological study, laboratory biomarker analysis.
干预措施: laboratory biomarker analysis (Other)
Phase 2 recurrent malignant gliomas and nonprogressive GBM
Phase II: Patients not concurrently receiving EIAEDs are treated with erlotinib as above at a predetermined dose (150mg/day.
patients requiring surgery treated 7 days prior to tumor removal (150mg/day)
PK analysis and effects of erlotinib on epidermal growth factor receptor (EGFR)
erlotinib hydrochloride given orally
Other: pharmacological study, laboratory biomarker analysis.
干预措施: pharmacological study (Other)
结局指标
主要结局
Define Maximum Tolerated Dose (MTD) of Erlotinib by Phase 1 Cohorts
时间窗: cycle 1 - 28 days
standard 3+3 dose escalation design 3 patients in each dose level, observed for 28 days before enrollment to next level. if none of the patients experienced DLT dose escalated, if 1 of 3 experienced DLT 3 more enrolled at that level, if none of the 3 additional pts had DLT escalate to next level, if one or more of the additional pts experienced DLT, the MTD was exceeded and 3 more patients were treated at the next lower dose (if only 3 pts treated at the lower dose). The MTD is the dose at which 0/3 or 1/6 patients have experienced a DLT with the next higher dose having at least 2/3 or 2/6 patients encountering DLT.
6 Months Progression-free Survival in Recurrent Malignant Gliomas (Phase II)
时间窗: 6 months
Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over BL if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Number of Dose Limiting Toxicity (DLT) Each Dose Level Phase I
时间窗: 28 days
DLT Definition: any grade 3 thrombocytopenia and grade 4 anemia and neutropenia; any non-hematologic grade 3 toxicity; failure to recover from toxicities to be eligible for re-treatment with erlotinib within 2 weeks of the last dose of erlotinib.
次要结局
- Overall Survival Newly Diagnosed GBM Post RT(2 years)
- 1 Year Survival - Phase II Newly Diagnosed GBM Post RT(At 1 year)
- Peak Plasma Concentration Per Dose Level Phase I (on Anticonvulsants) -(baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5)
- Estimation of the Area Under the Curve Per Dose Level Phase I (on Anticonvulsants) -(baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5)
- Percent of Participants With a Grade 3 or 4 Adverse Events Phase 1(1 year)
- Percent of Patients With One or More Grade 3-5 Toxicity Described Based on the CTC Severity Grading Phase II(Up to 1 year)
- Response Rate (Complete or Partial Response) Graded Using Modified RECIST Criteria Phase II(At 1 year)
- Time of Peak Plasma Concentration Per Dose Level Phase I (on Anticonvulsants) -(baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1.)
- Time to Peak Plasma Concentration for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg -(baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5)
- Pharmacokinetics (Tissue) Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs(Pre-surgery and time of resection)
- Trough Level Per Dose Level Phase I (on Anticonvulsants) -(cycle 1 day eight)
- Estimation of Area Under the Curve for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg-(baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5)
- Peak Plasma Concentration Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg -(baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5)
- Trough Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg -(One sample on day 8 cycle 1)
- Pharmacokinetics (Plasma) Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs(Pre-surgery and time of resection)