A Phase II Study of Cixutumumab (IMC-A12) in Combination With Temsirolimus in Pediatric Patients With Recurrent or Refractory Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 76
- 主要终点
- Objective Response Rate (PR or CR) by Response Evaluation Criteria in Solid Tumors (RECIST).
研究概览
简要总结
This phase II trial studies how well cixutumumab and temsirolimus work in treating patients with recurrent or refractory sarcoma. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cixutumumab and temsirolimus together may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the objective response rate to the combination of cixutumumab and temsirolimus in patients with relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, or non-rhabdomyosarcoma soft tissue sarcoma.
II. To further describe the toxicities (including dose-limiting toxicities) of cixutumumab and temsirolimus administered on this schedule.
SECONDARY OBJECTIVES:
I. To assess the progression-free survival for patients treated in each disease stratum with this drug combination.
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
- 1 Year 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with any of the following tumors who have experienced relapse following front-line therapy, or who are refractory to front-line therapy, are eligible:
- •Osteosarcoma
- •Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET)
- •Rhabdomyosarcoma
- •Non-rhabdomyosarcoma soft tissue sarcoma
- •Patients must have had histologic verification of malignancy at original diagnosis or relapse
- •All patients are required to submit archival tumor samples for immunohistochemical analysis (either paraffin-embedded tumor blocks or unstained slides)
- •Tissue samples collected at original diagnosis or at relapse or at any subsequent resections or biopsies should be available and ready for shipment to the Biopathology Center (BPC) at time of study enrollment; the samples are required even if tissue samples have previously been sent to the BPC for other purposes or studies; blocks or slides should be shipped to the BPC within 7 days of study enrollment
- •Patients must have radiographically measurable disease
- •Measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 10 mm in at least one dimension (CT scan slice thickness no greater than 5 mm)
- •The following do not qualify as measurable disease:
- •Malignant fluid collections (e.g., ascites, pleural effusions)
- •Bone marrow infiltration
- •Lesions only detected by nuclear medicine studies (e.g., bone, gallium, or positron emission tomography [PET] scans)
- •Elevated tumor markers in plasma or cerebrospinal fluid(CSF)
- •Previously radiated lesions that have not demonstrated clear progression post radiation
- •Leptomeningeal lesions that do not meet the measurements noted above
- •Patient?s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- •Patients with known central nervous system metastases are excluded unless treated surgically or with radiotherapy and stable with no recurrent lesions for at least 3 months
- •Patients must have a Lansky or Karnofsky performance status score of ? 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients ? 16 years of age
- •Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- •For patients with solid tumors without bone marrow involvement:
- •Peripheral absolute neutrophil count (ANC) ? 1,000/?L
- •Platelet count ? 100,000/?L (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment)
- •Hemoglobin ? 8.0 g/dL (may receive red blood cell [RBC] transfusions)
- •For patients with solid tumors and known bone marrow metastatic disease:
- •ANC ? 750/?L
- •Platelet count ? 50,000/?L (may receive platelet transfusions)
- •Hemoglobin ? 8.0 g/dL (may receive RBC transfusions)
- •For patients with known bone marrow metastatic disease, transfusions are permitted to meet both platelet and hemoglobin criteria; patients must not be known to be refractory to red blood cell or platelet transfusions
- •Creatinine clearance or radioisotope GFR ? 70 mL/min OR a serum creatinine based on age/gender as follows:
- •0.6 mg/dL (1 to < 2 years of age)
- •0.8 mg/dL (2 to < 6 years of age)
- •1.0 mg/dL (6 to < 10 years of age)
- •1.2 mg/dL (10 to < 13 years of age)
- •1.5 mg/dL (males) or 1.4 mg/dL (females) (13 to < 16 years of age)
- •1.7 mg/dL (males) or 1.4 mg/dL (females) ( ? 16 years of age)
- •Total bilirubin ? 1.5 times upper limit of normal (ULN)
- •Serum glutamic pyruvate transaminase(SGPT) (alanine aminotransaminase [ALT]) ? 2.5 times ULN (for the purpose of this study, the ULN for SGPT is 45 U/L)
- •Serum albumin ? 2 g/dL
- •Patients with seizure disorder may be enrolled if receiving non-enzyme-inducing anticonvulsants and well controlled
- •Patients with known type I or type II diabetes mellitus are not eligible
- •Serum glucose values must be within the normal limits for age; if the initial blood glucose is a random sample that is outside normal limits, then a follow-up fasting blood glucose should be obtained and must be within the normal limits for age
- •Serum cholesterol levels must be < grade 2 (< 300 mg/dL), and serum triglyceride levels must be < grade 2 (< 2.5 times ULN)
- •Patients who are pregnant or breast-feeding are not eligible for this study
- •Negative pregnancy tests must be obtained in girls who are post-menarchal
- •Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of the study and for 3 months after the last dose of cixutumumab
- •Patients who have an uncontrolled infection are not eligible
- •Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible
- •See Disease Characteristics
- 另有 17 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (cixutumumab, temsirolimus)
Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Cixutumumab (Biological)
Treatment (cixutumumab, temsirolimus)
Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (cixutumumab, temsirolimus)
Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Temsirolimus (Drug)
结局指标
主要结局
Objective Response Rate (PR or CR) by Response Evaluation Criteria in Solid Tumors (RECIST).
时间窗: 6 cycles (168 days)
Per Response evaluation criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR)= CR+PR. The combination of sufficient activity is considered if the true response rate is 35% or greater.
Number of Cycles of Toxicity
时间窗: Duration of protocol therapy - Up to 25 cycles (700 days)
The number of patients-cycles where CTC Version 4 grade 3 or higher increased Alanine aminotransferase was observed
次要结局
- Expression Levels of IGF-1R, Insulin Receptor, ERK, RON, and mTOR(Baseline)
- Number of Patients With Detectable Bone Marrow Micrometastatic Disease Estimated as the Proportion of Eligible Patients Entered Into the Ewing Sarcoma Stratum Who Have Detectable Tumor Cells in the Marrow at Enrollment(Baseline)
- Progression-free Interval(10 months after enrollment)