Combination of External Beam Radiotherapy with 153Sm-EDTMP to Treat High Risk Osteosarcoma and Patients with Solid Tumors Metastatic to Bone
Johns Hopkins Kimmel Cancer Center in Baltimore
This research is being done to see whether radiation with the study drug 153Sm-EDTMP can stop or reverse the growth of osteosarcoma. The usual treatment for osteosarcoma includes surgery to remove as much tumor as possible, and chemotherapy to kill any cancer cells that have escaped from the tumor. For patients that cannot have surgery or chemotherapy, we are trying to find other ways to reduce tumor growth.Objectives: To assess the clinical response of high-risk osteogenic sarcoma to high-dose 153Sm-EDTMP and external beam radiotherapy.To describe the toxicity and long-term effects of combined infusional 153Sm-EDTMP and external beam radiation therapy. To observe overall survival and time to progression in patients treated with combined infusional 153Sm-EDTMP and external beam radiation therapy, and model and relationship between total absorbed dose and progression.To image tumors using [18F] Fluoromisonidazole (18F-MISO) PET scanning before and after treatment, and compare with clinical response as measured by radiographic imaging and/or histology.To describe the distribution of absorbed doses delivered to each targeted lesion and the distribution of lesion equivalent uniform dose delivered to each patient.To determine dosimetry measurements after initial tracer dosing, predict target total radiation exposure to tumor based on linear kinetics previously described, and calculate a subsequent combined treatment dose.
Patients must be between age 13 and 65 (inclusive) and have unresectable primary tumor or metastases. Patients must have measurable disease as demonstrated by a positive Bone Scan (not all lesions must be positive on bone scan). Patient must have good organ function with good blood counts and be up and out of bed at least 50% of the day. Patients may not be pregnant or breastfeeding. Patients who have had prior radiation therapy to all areas of current active disease are ineligible.
This study treatment is administered in the outpatient setting. Patient must be willing/able to adhere to multiple clinic visits, some of which may be lengthy (full days). Patient will come to clinic for blood/urine tests, doctor/nurse visits and various radiology imaging appointments. After consent and review/verification of eligibility, patient will receive 2 doses of 153Sm-EDTMP. The first dose is a low tracer infusion which is used to determine the distribution of dose delivered to the tumor and the surrounding normal tissues. Within approximately 7 days, using the dosimetric results from the tracer infusion, a combined treatment plan will be designed aimed at delivering the target dose to the entire tumor. The second treatment infusion of 153SM-EDTMP will be administered at the maximally tolerated dose permitting recovery of myelosuppression with auto-stem cell infusion. Approximately 14 days after administration of the treatment dose, previously harvested autologous peripheral blood or bone marrow stem cells will be infused in order to ameliorate the expected myelosuppression. Patients who do not stem cells available, will receive standard of care stem cell harvest preparation inclusive of chemotherapy Ifosfamide for 5 consecutive days, with MESNA. The radiotherapy portion of the combined plan will be delivered according to the judgment of the treating radiation oncologist. Patients will be followed for up to 48 months for toxicity, inclusive of blood work, radiology imaging, doctor/nurse visits.
06/26/2016 05:03 AM