A Phase I, Open Label, Maximum Tolerated Dose-Finding Study to Evaluate the Safety and Tolerability of 90Y-DOTA-tyr3-Octreotide Administered by Intravenous Infusion to Children With Refractory Somatostatin-Receptor Positive Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Establish the three-cycle maximum-tolerated dose of 90Y-DOTA-tyr3-Octreotide
研究概览
简要总结
RATIONALE: Radiolabeled octreotide can locate tumor cells and deliver radioactive tumor-killing substances to them without harming normal cells.
PURPOSE: This phase I trial is to study the safety and effectiveness of radiolabeled octreotide in treating children who have advanced or refractory solid tumors.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of yttrium Y 90-DOTA-tyr3-octreotide in children with advanced or refractory somatostatin receptor-positive tumors.
- Determine the short-term and long-term safety and the serious adverse-event profiles of this drug in these patients.
- Determine any potential antitumor effect of this drug in these patients.
- Correlate level of somatostatin receptor type 2 expression with response in patients treated with this drug.
OUTLINE: This is a dose-escalation study.
Patients receive yttrium Y 90-DOTA-tyr3-octreotide IV over 5-10 minutes on day 1. Treatment repeats every 6 weeks for up to 3 courses in the absence of unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of yttrium Y 90-DOTA-tyr3-octreotide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.
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
- 2 Years 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically or cytologically confirmed malignant neoplasm
- •Not amenable to standard therapy or has failed existing first- and second-line therapies
- •Tumor positive for somatostatin receptors by OctreoScan within the past 4 weeks
- •At least 1 measurable lesion
- •Lesions that have been previously irradiated must demonstrate progression since radiation
- •At least 1 measurable somatostatin receptor-positive lesion that has not been irradiated within the past 4 weeks AND has not had full craniospinal radiation within the past 3 months
- •Bone marrow with at least 40% cellularity OR at least 20% cellularity with one million CD34+ stem cells/kg stored
- •No diffuse bone marrow involvement by OctreoScan scintigraphy
- •PATIENT CHARACTERISTICS:
- •Performance status
- •COG 0-2 OR
- •Karnofsky 60-100% OR
- •Lansky 60-100%
- •Life expectancy
- •2-12 months
- •Hematopoietic
- •See Disease Characteristics
- •Absolute neutrophil count at least 1,000/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin less than 1.5 times normal
- •AST and ALT less than 2.5 times upper limit of normal
- •Creatinine no greater than 1 mg/dL (children less than 5 years of age)
- •Creatinine less than 1.2 mg/dL (children 5 to 10 years of age)
- •Creatinine less than 1.7 mg/dL (children over 10 years of age) AND
- •Glomerular filtration rate at least 80 mL/min/m^2
- •Cardiovascular
- •Shortening fraction at least 28% by echocardiogram
- •Ejection fraction at least 50% by bi-plane method of echocardiogram
- •No prior congestive heart failure unless ejection fraction at least 40%
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •No symptomatic congestive heart failure
- •No other concurrent malignancy
- •No other significant uncontrolled medical, psychiatric, or surgical condition that would preclude study compliance
- •No antibodies to yttrium Y 90-DOTA-tyr3-octreotide or octreotide
- •No prior allergic reactions to compounds of similar chemical or biologic composition to yttrium Y 90-DOTA-tyr3-octreotide
- •No ongoing or active infection
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 6 months after study participation
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •Not specified
- •Chemotherapy
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- •Endocrine therapy
- •More than 28 days since prior long-acting somatostatin analogues
- •No concurrent somatostatin analogues 12 hours before or 12 hours after study drug administration
- •Concurrent hormonal therapy (other than somatostatin analogue) allowed provided patient received hormonal therapy for at least 2 months and has stable disease or progressive disease
- 另有 10 项未显示
排除标准
- 未提供
研究组 & 干预措施
90Y-DOTA-tyr3-OCTREOTIDE
Dose escalation will proceed so that the single-cycle and three-cycle maximum tolerated doses of 90Y-DOTA-tyr3-Octreotide can be determined. The initial dose of 90Y-DOTA-tyr3-Octreotide to be administered is 30 mCi/m2 in each of three cycles. Dose escalation will proceed in 10 mCi/m2 intervals and will be permitted for the next cohort of subjects pending completion of Cycle 3 by 2 members of the previous cohort with no DLTs. A DLT is defined as a Grade 3 renal toxicity, Grade 4 bone marrow toxicity, or any other Grade 3 toxicity whether or not related to study drug and regardless of duration. Lymphopenia will not be used to define a DLT.
干预措施: 90Y-DOTA-tyr3-OCTREOTIDE (Radiation)
结局指标
主要结局
Establish the three-cycle maximum-tolerated dose of 90Y-DOTA-tyr3-Octreotide
时间窗: 6 weeks per cycle
Establish the three-cycle maximum-tolerated dose of 90Y-DOTA-tyr3-Octreotide administered by intravenous infusion to children with refractory somatostatin-receptor positive tumors based upon the 6 week/cycle dose-limiting-toxicity profile.
Evaluate the short term and long term safety (mild/moderate/severe/life-threatening adverse events, premature discontinuations and serious adverse events)
时间窗: short term (6 weeks/cycle); long term (4-6 mos./cycle)
2. Evaluate the short-term (6 weeks/cycle) and long term (4-6 months) safety (mild/moderate/severe/life-threatening adverse events, premature discontinuations and serious adverse events) serious adverse event profile of three-cycles of 90Y-DOTA-tyr3-Octreotide administered by intravenous infusion to children with refractory somatostatin-receptor positive tumors.
次要结局
未报告次要终点
研究者
O'Dorisio, M S
Professor
University of Iowa