A Dose Finding Study of CycloSam® (153Sm-DOTMP) Combined With External Beam Radiotherapy to Treat High Risk Osteosarcoma and Other Solid Tumors Metastatic to Bone
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Maximally Tolerated Dose
研究概览
简要总结
This is a dose finding study of a novel radiopharmaceutical agent, 153Sm-DOTMP. It will be studied alone and then in combination with external beam radiotherapy. The study design includes six cohorts, Levels 1-6. The first three cohorts of participants will receive 153Sm-DOTMP alone, and if this is determined to be safe, subsequent cohorts will receive the radiopharmaceutical followed by external beam radiotherapy.
详细描述
This is a dose escalation study of a new radiopharmaceutical agent, 153Sm-DOTMP. Eligible participants will have osteosarcoma metastatic to bone, other solid tumors with bone metastases, or an unresectable localized osteosarcoma. Because of anticipated prolonged myelosuppression, participants will have a peripheral blood stem cell harvest. They will then be treated with 2 doses of 153Sm-DOTMP given 7 days apart. Twenty-four days after the initial dose, stem cells will be reinfused if needed. The first three cohorts of participants will receive only radiopharmaceutical. If Dose Level 3 is not the maximally tolerated dose (MTD), subsequent dose levels will include external beam radiotherapy, administered beginning on Day 15. The dose of external beam radiotherapy will be determined by dosimetry studies performed after each administration of study agent, and will be targeted to a tumoricidal dose of radiation. All participants will have disease re-evaluation 30 days following completion of all study treatments, and then at 4, 6, 8, and 12 months, unless they experience disease progression.
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
- 15 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of a solid tumor metastatic to bone, or a histologically confirmed diagnosis of osteosarcoma with either an unresectable primary tumor or metastases (including tumors with an intralesional resection).
- •Measurable disease on anatomic imaging that is also avid for phosphonate compounds as demonstrated by a positive 99mTc diphosphonate bone scan.
- •Adequate renal function, defined as a measured creatinine clearance >70 ml/min/1.73 m2 or normal radioisotope glomerular filtration rate (GFR).
- •Adequate hematologic function, defined as a platelet count > 50,000 cells/mm3 and an absolute neutrophil count (ANC) > 500 cells/mm3
- •Life expectancy of at least 8 weeks.
- •Karnofsky performance status > 50%
- •Subject must have adequately recovered from the effects of any prior chemotherapy, as determined by the treating physician and study team, based in part on organ function defined above. Toxicities from previous therapies must have recovered to Common Terminology Criteria for Adverse Events (CTCAE) 4.0 grade 2 or better.
- •Patients must have previously received effective treatment for their underlying disease and have no potentially curative options available.
排除标准
- •Subject has received prior radiotherapy to all known areas of current active disease or has a known contraindication to receiving radiotherapy.
- •Subject is pregnant or breastfeeding.
- •Patient is sexually active and does not agree to use accepted, effective forms of contraception.
研究组 & 干预措施
Dose Escalation Arm
Dose Levels 1-3 will consist of treatment with radiopharmaceutical (153Sm-DOTMP) alone. If the maximally tolerated dose (MTD) has not been reached at Level 3, external beam radiotherapy will be added to each of Levels 4-6. Participants enrolled on Dose Levels 4-6 will be treated with external beam radiotherapy to all radiographically evident sites of disease. If an MTD has not been determined at Level 6, the study will end and Dose Level 6 will be declared the Recommended Phase 2 Dose.
Participants will be given prophylactic / supportive treatment protocols including Calcium Carbonate, mozobil, and neupogen injectable product.
干预措施: 153Sm-DOTMP (Drug)
Dose Escalation Arm
Dose Levels 1-3 will consist of treatment with radiopharmaceutical (153Sm-DOTMP) alone. If the maximally tolerated dose (MTD) has not been reached at Level 3, external beam radiotherapy will be added to each of Levels 4-6. Participants enrolled on Dose Levels 4-6 will be treated with external beam radiotherapy to all radiographically evident sites of disease. If an MTD has not been determined at Level 6, the study will end and Dose Level 6 will be declared the Recommended Phase 2 Dose.
Participants will be given prophylactic / supportive treatment protocols including Calcium Carbonate, mozobil, and neupogen injectable product.
干预措施: External beam radiotherapy. (Radiation)
Dose Escalation Arm
Dose Levels 1-3 will consist of treatment with radiopharmaceutical (153Sm-DOTMP) alone. If the maximally tolerated dose (MTD) has not been reached at Level 3, external beam radiotherapy will be added to each of Levels 4-6. Participants enrolled on Dose Levels 4-6 will be treated with external beam radiotherapy to all radiographically evident sites of disease. If an MTD has not been determined at Level 6, the study will end and Dose Level 6 will be declared the Recommended Phase 2 Dose.
Participants will be given prophylactic / supportive treatment protocols including Calcium Carbonate, mozobil, and neupogen injectable product.
干预措施: Calcium Carbonate (Drug)
Dose Escalation Arm
Dose Levels 1-3 will consist of treatment with radiopharmaceutical (153Sm-DOTMP) alone. If the maximally tolerated dose (MTD) has not been reached at Level 3, external beam radiotherapy will be added to each of Levels 4-6. Participants enrolled on Dose Levels 4-6 will be treated with external beam radiotherapy to all radiographically evident sites of disease. If an MTD has not been determined at Level 6, the study will end and Dose Level 6 will be declared the Recommended Phase 2 Dose.
Participants will be given prophylactic / supportive treatment protocols including Calcium Carbonate, mozobil, and neupogen injectable product.
干预措施: Mozobil (Drug)
Dose Escalation Arm
Dose Levels 1-3 will consist of treatment with radiopharmaceutical (153Sm-DOTMP) alone. If the maximally tolerated dose (MTD) has not been reached at Level 3, external beam radiotherapy will be added to each of Levels 4-6. Participants enrolled on Dose Levels 4-6 will be treated with external beam radiotherapy to all radiographically evident sites of disease. If an MTD has not been determined at Level 6, the study will end and Dose Level 6 will be declared the Recommended Phase 2 Dose.
Participants will be given prophylactic / supportive treatment protocols including Calcium Carbonate, mozobil, and neupogen injectable product.
干预措施: Neupogen Injectable Product (Drug)
结局指标
主要结局
Maximally Tolerated Dose
时间窗: MTD will be determined based on DLTs experienced by participants during the first 42 days after administration of 153Sm-DOTMP for Dose Levels 1-3 and during the first 70 days after administration for Dose Levels 4-6
The maximally tolerated dose (MTD) of 153Sm-DOTMP will be determined. The MTD will be defined as the dose that produces a dose limiting toxicity (DLT) in 30% of the participants. The dose limiting toxicity is the dosage at which side effects are serious enough to prevent an increase in dose or level of that treatment. DLTs will be defined as any grade 3, 4, or 5 non-hematologic toxicity experienced during a 42-70 day observation window.
次要结局
- Overall Survival(From date of enrollment until date of death from any cause, assessed up to 60 months)
- Time To Progression(Participants will be evaluated 4, 8, and 12 months after treatment.)
- Clinical Response Rate 30 days post treatment(30 days post treatment)
- Clinical Response Rate 4 months post treatment(4 months post treatment)
- Clinical Response Rate 12 months post treatment(12 months post treatment)
- Clinical Response Rate 8 months post treatment(8 months post treatment)