A Randomized, Phase 2 Study of Single-agent Erlotinib Versus Oral Etoposide in Patients With Recurrent or Refractory Pediatric Ependymoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 25
- 试验地点
- 28
- 主要终点
- Percentage of Participants With an Objective Response
研究概览
简要总结
This is a phase 2 study to evaluate the efficacy of single-agent erlotinib versus oral etoposide in patients with recurrent or refractory pediatric ependymoma.
详细描述
This is a phase 2 study involving a 1:1 randomization of 40 patients with recurrent or refractory pediatric ependymoma who will receive either erlotinib or oral etoposide.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Recurrent of refractory ependymoma or subependymoma
- •Performance Status (PS): Lansky ≥ 50% for patients ≤ 10 years of age or Karnofsky ≥ 50% for patients >10 years of age
- •Measurable disease, defined as 1 measurable lesion that can be accurately measured in 2 planes that has not received radiation therapy within 12 weeks
- •Recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy
- •≥ 1 year to ≤ 21 years
- •Serum creatinine for patients ≤ 5 years in age is ≤ 0.8 mg/dL or Creatinine Clearance/Glomerular Filtration Rate (GFR) ≥ 70 mL/min/m^2
- •Serum creatinine for patients > 5 and ≤ 10 years in age is ≤ 1.0 mg/dL or Creatinine Clearance/GFR ≥ 70 mL/min/m^2
- •Serum creatinine for patients > 10 and ≤ 15 years in age is ≤ 1.2 mg/dL or Creatinine Clearance/GFR ≥ 70 mL/min/m^2
- •Serum creatinine for patients > 15 years in age is ≤ 1.5 mg/dL or Creatinine Clearance/GFR ≥ 70 mL/min/m^2
- •Total bilirubin is ≤ 1.5 x upper limit of normal for age
- •Alanine aminotransferase (ALT) ≤ 3 x upper limit of normal
- •Absolute neutrophil count > 1000/µL
- •Platelet count > 100,000/µL
- •Hemoglobin > 8 gm/dL
- •Neurologically stable for at least 7 days prior to randomization
- •If receiving corticosteroids, patients must be on a stable or decreasing dose for at least 7 days before randomization
- •Patients of reproductive potential must agree to proactive effective contraceptive measures for the duration of the study and for at least 90 days after completion of study drug
排除标准
- •Previously received epidermal growth factor receptor (EGFR)-targeted therapy
- •Previously received oral etoposide
- •Received craniospinal radiotherapy within 24 weeks prior to randomization
- •Received field radiotherapy to the target lesion within 12 weeks prior to randomization
- •Received symptomatic metastatic disease within 14 days prior to randomization
- •Received myelosuppressive chemotherapy within 21 days before randomization
- •Received growth factors within 7 days prior to randomization
- •Participating in another investigational drug trial
- •Received a biologic agent within 7 days prior to randomization
- •Received a monoclonal antibody within 28 days prior to randomization
- •Taking cytochrome P450 (CYP)3A4 or CYP1A2 inhibitors/inducers within 14 days prior to randomization
- •Taking proton pump inhibitors within 14 days prior to randomization
- •Smoking during treatment
- •Pregnant or breast-feeding females
研究组 & 干预措施
Erlotinib
Erlotinib was administered orally at a dose of 85 mg/m^2 per day continuously until either progression, death, patient request or investigator decision to discontinue study drug or intolerable toxicity.
干预措施: erlotinib (Drug)
Etoposide
Etoposide 50 mg/m^2 per day was administered orally for 21 days followed by a 7-day rest period until either progression, death, patient request or investigator decision to discontinue study drug or intolerable toxicity.
干预措施: etoposide (Drug)
结局指标
主要结局
Percentage of Participants With an Objective Response
时间窗: From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.
Objective response is defined as a best overall response of complete response (CR) or partial response (PR), evaluated using modified International Society of Pediatric Oncology Brain, Tumor Subcommittee for the Reporting of Trials criteria. Response was confirmed at least 28 days after the first assessment where the response criteria were met. Response was assessed by magnetic resonance imaging (MRI) every 8 weeks. CR: • Complete disappearance of all enhancing tumor and mass effect • On a stable or decreasing dose of corticosteroids (or receiving only adrenal replacement doses) • Stable or improving neurologic examination sustained for ≥ 4 weeks • If cerebral spinal fluid (CSF) evaluation was positive, it must become negative (confirmed at least 2 times at consecutive samplings). PR: • ≥ 50% reduction in tumor size by bi-dimensional measurement • On a stable or decreasing dose of corticosteroids • Stable or improving neurologic examination sustained for ≥ 4 weeks.
次要结局
- Duration of Response(From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.)
- Percentage of Participants With a Minor Response(From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.)
- Percentage of Participants With Disease Control(From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.)
- Progression Free Survival (PFS)(From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.)
- Percentage of Participants With Prolonged Stable Disease(From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.)
- Duration of Stable Disease(From randomization until the end of treatment. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.)
- Overall Survival (OS)(From randomization up to 12 months after the last dose. Median duration of follow-up was 12.9 months for erlotinib and 14.4 months for etoposide.)
- Safety Assessed Through Evaluation of Physical Exams, Vital Signs, Clinical Laboratory Tests and Adverse Events (AEs)(From the date of first dose of study drug until 30 days after the last dose. The median time on treatment was 52 days for erlotinib and 58 days for etoposide.)
- Area Under the Curve From Time 0 to 24 Hours Post-dose for Erlotinib(Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose.)
- Maximum Observed Plasma Concentration of Erlotinib (Cmax)(Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose.)
- Time to Maximum Observed Plasma Concentration of Erlotinib (Tmax)(Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose.)
- Apparent Body Clearance (CL/F) of Erlotinib(Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose.)
- Apparent Volume of Distribution (Vz/F) of Erlotinib(Day 14 predose and 0.5 to 1.5 hours, 2 to 3 hours and 4 to 8 hours post-dose.)