Feasibility of High-dose Iodine-131-metaiodobenzylguanidine Therapy for High-risk Neuroblastoma Preceding Myeloablative Chemotherapy and Hematopoietic Stem Cell Transplantation: a Study Protocol.

OBJECTIVES: High-risk neuroblastoma is a childhood cancer with poor prognosis despite modern multimodality therapy. Internal radiotherapy using 131I-metaiodobenzylguanidine (MIBG) is effective for treating the disease even if it is resistant to chemotherapy. The aim of this study is to evaluate the safety and efficacy of 131I-MIBG radiotherapy combined with myeloablative high-dose chemotherapy and hematopoietic stem cell transplantation. METHODS: Patients with high-risk neuroblastoma will be enrolled in this study. A total of 8 patients will be registered. Patients will receive 666 MBq/kg of 131I-MIBG and after safety evaluation will undergo high-dose chemotherapy and hematopoietic stem cell transplantation. Autologous and allogeneic stem cell sources will be accepted. After engraftment or 28 days after hematopoietic stem cell transplantation, the safety and response will be evaluated. CONCLUSION: This is the first prospective study of 131I-MIBG with high-dose chemotherapy and hematopoietic stem cell transplantation in Japan. The results will be the basis of a future nationwide clinical trial.

A phase I clinical trial for [131I]meta-iodobenzylguanidine therapy in patients with refractory pheochromocytoma and paraganglioma: a study protocol.

Objective Pheochromocytoma and paraganglioma (PPGLs) are rare neuroendocrine tumors derived from the adrenal medulla or extra-adrenal paraganglioma from extra-adrenal chromaffin tissue. Although malignant PPGLs has miserable prognosis, the treatment strategy remains to be established. An internal radiation therapy using [131I]meta-iodobenzylguanidine (131I-mIBG) called MIBG therapy has been attempted as one of the systemic treatment of malignant PPGLs. The aim of this study is therefore to evaluate the safety and the efficacy of MIBG therapy for refractory PPGLs. Methods Patients with refractory PPGLs will be enrolled in this study. The total number of patients for registration is 20. The patients receive a fixed dose of 7,400 MBq of 131I-mIBG. Adverse events are surveyed during 20 weeks after 131I-mIBG injection and all severe adverse events will be documented and reported in detail in accordance with the Common Terminology Criteria for Adverse Events (CTCAE). Examination and imaging diagnosis are performed in 12 weeks after 131I-mIBG injection for the evaluation of therapeutic effect in accordance with the Response Evaluation in Solid Tumours (RECIST). Conclusion The current study is the first multi-institutional prospective study of MIBG therapy and thereby will play a significant role in improving the patients' prognosis of refractory PPGLs. J. Med. Invest. 64: 205-209, August, 2017.

Phase I/II study of alectinib in lung cancer with RET fusion gene: study protocol.

BACKGROUND: The rearranged during transfection (RET) fusion gene was discovered as a driver oncogene in 1-2% of non-small cell lung cancers (NSCLCs). Alectinib is an approved anaplastic lymphoma kinase (ALK) inhibitor that may also be effective for RET fusion-positive NSCLC. METHODS/DESIGN: RET fusion-positive NSCLC patients treated with at least one regimen of chemotherapy are being recruited. In step 1, alectinib (600 or 450 mg, twice daily) will be administered following a 3+3 design. The primary endpoint is safety. In step 2, alectinib will be administered at the recommended dose (RD) defined by step 1. The primary endpoint is the response rate of RET inhibitor treatment-naïve patients. CONCLUSION: This is the first study to investigate the safety and preliminary efficacy of alectinib in RET fusion-positive NSCLC patients. If successful, alectinib treatment may lead to substantial and important changes in the management of NSCLC with RET fusion genes. J. Med. Invest. 64: 317-320, August, 2017.