Study of the TEM-1 Antibody, MORAb-004 (IND# 103821), in Children With Recurrent or Refractory Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Morphotek
- 入组人数
- 27
- 试验地点
- 40
- 主要终点
- MTD, defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicities (DLT) graded according to the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
研究概览
简要总结
This phase I trial studies the side effects and best dose of MORAb-004 in treating young patients with recurrent or refractory solid tumors or lymphoma. Monoclonal antibodies, such as MORAb-004, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them
详细描述
PRIMARY OBJECTIVES:
I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of MORAb-004 (anti-endosialin/TEM1 monoclonal antibody MORAb-004) administered as an intravenous infusion every week to children with refractory solid tumors.
II. To define and describe the toxicities of MORAb-004 administered on this schedule.
III. To characterize the pharmacokinetics of MORAb-004 in children with refractory cancer.
IV. To monitor for the development of human anti-human antibody (HAHA) in children receiving MORAb-004.
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
- 13 Months 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with relapsed or refractory solid tumors or lymphoma, excluding central nervous system (CNS) tumors, are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse; (patients with primary CNS tumors, known CNS metastases, or a prior history of CNS metastases are not eligible)
- •Patients must have either measurable or evaluable disease
- •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
- •Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; Note: 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
- •Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
- •At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
- •At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
- •At least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
- •At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
- •At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
- •At least 14 days after local palliative radiotherapy (XRT) (small port); at least 150 days must have elapsed if prior total-body irradiation (TBI), craniospinal XRT or if >= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
- •No evidence of active graft vs. host disease and at least 56 days must have elapsed after transplant or stem cell infusion
- •For patients with solid tumors without known bone marrow involvement:
- •Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
- •Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
- •For patients with known bone marrow metastatic disease:
- •ANC >= 750/mm^3
- •Platelet count >= 75,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
- •Patients with known bone marrow metastatic disease will not be evaluable for hematologic toxicity; these patients must not be known to be refractory to red cell or platelet transfusion; at least 5 of every cohort of 6 patients with a solid tumor or lymphoma must be evaluable for hematologic toxicity; if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
- •Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70ml/min/1.73 m^2 OR a serum creatinine based on age/gender as follows:
- •=< 0.6 mg/dL for patients age 1 to < 2 years
- •=< 0.8 mg/dL for patients age 2 to < 6 years
- •=< 1 mg/dL for patients age 6 to 10 2 years
- •=< 1.2 mg/dL for patients age 10 to < 13 years
- •=< 1.4 mg/dL for female patients age >= 13 years
- •=< 1.5 mg/dL for male patients age 13 to < 16 years
- •=< 1.7 mg/dL for male patients age >= 16 years
- •Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
- •Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
- •Serum albumin >= 2 g/dL
- •Activated partial thromboplastin time (aPTT) and prothrombin time (PT) =< 1.5 x ULN
- •All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
- •Tissue blocks or slides must be sent per Section 8.
- •If tissue blocks or slides are unavailable, the study chair must be notified prior to enrollment.
排除标准
- •Pregnant or breast-feeding women will not be entered on this study; 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
- •Patients receiving chronic systemic corticosteroids are not eligible
- •Patients who are currently receiving another investigation drug are not eligible
- •Patients who are currently receiving other anti-cancer agents are not eligible
- •Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
- •Patients who have known human immunodeficiency virus (HIV), viral hepatitis, or an uncontrolled infection are not eligible
- •Patients with primary CNS tumors are excluded
- •Patients with prior history of or known metastatic CNS disease involvement are excluded; (Note: CNS imaging for patients without a known history of CNS disease is only required if clinically indicated)
- •Patients who have had or are planning to have the following invasive procedures are not eligible:
- •Major surgical procedure, laparoscopic procedure, open biopsy or significant traumatic injury within 28 days prior to enrollment
- •Central line placement or subcutaneous port placement is not considered major surgery but must be placed at least 3 days prior to enrollment for external lines (e.g. Hickman or Broviac) and at least 7 days prior to enrollment for subcutaneous port
- •Core biopsy within 7 days prior to enrollment
- •Fine needle aspirate within 7 days prior to enrollment
- •Patients who have received prior solid organ transplantation 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
- •Patients with history of clinically significant bleeding risk (including evidence of active bleeding: intratumoral hemorrhage by current imaging, or bleeding diathesis; bleeding/coagulation disorder; active fracture; non-healing wound; and active gastric ulcer) are not eligible
研究组 & 干预措施
Treatment (MORAb-004)
Patients receive anti-endosialin/TEM1 monoclonal antibody MORAb-004 IV on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Treatment (MORAb-004)
Patients receive anti-endosialin/TEM1 monoclonal antibody MORAb-004 IV on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (MORAb-004)
Patients receive anti-endosialin/TEM1 monoclonal antibody MORAb-004 IV on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
干预措施: anti-endosialin/TEM1 monoclonal antibody MORAb-004 (Biological)
结局指标
主要结局
MTD, defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicities (DLT) graded according to the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
时间窗: Up to 4 weeks
Incidence of toxicities, graded according to NCI CTCAE version 4.0
时间窗: Up to 3 years
A descriptive summary of all toxicities will be reported.
次要结局
未报告次要终点