A Dose Finding Study of CycloSam® Combined With External Beam Radiotherapy

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

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.

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.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.