A single arm phase II study of bone-targeted Sn-117 m-DTPA in symptomatic castration-resistant prostate cancer with skeletal metastases
Abstract Background Several bone-seeking radionuclides have been developed for palliation of metastatic bone pain since 1956, however, so far radium-223 dichloride is the first and only Food and Drug Administration (FDA) approved targeted alpha therapy for metastatic castration-resistant prostate ca...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-022-09496-2 |
| _version_ | 1818274055255490560 |
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| author | Zin W. Myint Riham El Khouli Bryan Lemieux Donglin Yan William H. St. Clair Xiaoqi Liu Charles A. Kunos |
| author_facet | Zin W. Myint Riham El Khouli Bryan Lemieux Donglin Yan William H. St. Clair Xiaoqi Liu Charles A. Kunos |
| author_sort | Zin W. Myint |
| collection | DOAJ |
| description | Abstract Background Several bone-seeking radionuclides have been developed for palliation of metastatic bone pain since 1956, however, so far radium-223 dichloride is the first and only Food and Drug Administration (FDA) approved targeted alpha therapy for metastatic castration-resistant prostate cancer (mCRPC) based on ALSYMPCA phase 3 study. While radium-223 does improve pain and overall survival outcomes, the improvement can come at the expense of side effects such as bone marrow toxicity. The development of new and better treatment with long-standing pain relief is clearly an unmet medical need. Methods The study is a non-randomized phase II study. The study population consists of 25 patients with CRPC who had progressed on any lines of prior therapies and whose serum testosterone level is less than 50 ng/dl and have metastatic lesions to at least two bone sites, with at least one site that has clinically meaningful pain at baseline (≥ 4 on an 11-point intensity scale). Eligible patients will be given two cycles of Sn-117 m-DTPA every 8 weeks or 56 days. Treatment will be administered by slow IV injection over 5–10 min. Retreatment after two cycles is allowed if patients meet the following retreatment criteria. The primary objective is to evaluate the efficacy of Sn-117 m-DTPA on sustained pain response in patients with CRPC metastatic to at least two bone sites and at least one with clinically meaningful pain at baseline (≥ 4 on an 11-point pain intensity scale). Sustained pain response is defined as: 1) achieving pain index ≤ 3 within a 12-week period and 2) maintaining pain index ≤ 3 over a 16-week period. The secondary objectives are: safety and tolerability, measurement of Sn-117 m-DTPA activity by gamma-camera dosimetry scans, therapeutic efficacy, time to the first symptomatic skeletal event, duration of pain response, changes in PSA and ALP levels, patient-reported outcomes and progression free survival and overall survival. Discussion Sn-117 m-DTPA is a unique bone-targeting theranostic radiopharmaceutical agent that selectively binds most heavily to bone metastases sites. This study will be the first prospective phase II trial to assess the pain efficacy and anti-tumor activity of Sn-117 m-DTPA in mCRPC with at least one clinically meaningful pain at baseline. Trial registration. ClincialTrials.gov Identifier: NCT04616547. |
| first_indexed | 2024-12-12T22:07:46Z |
| format | Article |
| id | doaj.art-b8d6b4a8b9144750b21636db3b27a591 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-12T22:07:46Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-b8d6b4a8b9144750b21636db3b27a5912022-12-22T00:10:20ZengBMCBMC Cancer1471-24072022-04-012211910.1186/s12885-022-09496-2A single arm phase II study of bone-targeted Sn-117 m-DTPA in symptomatic castration-resistant prostate cancer with skeletal metastasesZin W. Myint0Riham El Khouli1Bryan Lemieux2Donglin Yan3William H. St. Clair4Xiaoqi Liu5Charles A. Kunos6Department of Medicine, Division of Medical Oncology, University of KentuckyDepartment of Nuclear Medicine, University of KentuckyDepartment of Radiation Safety, University of Kentucky Health CareMarkey Cancer Center, University of KentuckyMarkey Cancer Center, University of KentuckyMarkey Cancer Center, University of KentuckyMarkey Cancer Center, University of KentuckyAbstract Background Several bone-seeking radionuclides have been developed for palliation of metastatic bone pain since 1956, however, so far radium-223 dichloride is the first and only Food and Drug Administration (FDA) approved targeted alpha therapy for metastatic castration-resistant prostate cancer (mCRPC) based on ALSYMPCA phase 3 study. While radium-223 does improve pain and overall survival outcomes, the improvement can come at the expense of side effects such as bone marrow toxicity. The development of new and better treatment with long-standing pain relief is clearly an unmet medical need. Methods The study is a non-randomized phase II study. The study population consists of 25 patients with CRPC who had progressed on any lines of prior therapies and whose serum testosterone level is less than 50 ng/dl and have metastatic lesions to at least two bone sites, with at least one site that has clinically meaningful pain at baseline (≥ 4 on an 11-point intensity scale). Eligible patients will be given two cycles of Sn-117 m-DTPA every 8 weeks or 56 days. Treatment will be administered by slow IV injection over 5–10 min. Retreatment after two cycles is allowed if patients meet the following retreatment criteria. The primary objective is to evaluate the efficacy of Sn-117 m-DTPA on sustained pain response in patients with CRPC metastatic to at least two bone sites and at least one with clinically meaningful pain at baseline (≥ 4 on an 11-point pain intensity scale). Sustained pain response is defined as: 1) achieving pain index ≤ 3 within a 12-week period and 2) maintaining pain index ≤ 3 over a 16-week period. The secondary objectives are: safety and tolerability, measurement of Sn-117 m-DTPA activity by gamma-camera dosimetry scans, therapeutic efficacy, time to the first symptomatic skeletal event, duration of pain response, changes in PSA and ALP levels, patient-reported outcomes and progression free survival and overall survival. Discussion Sn-117 m-DTPA is a unique bone-targeting theranostic radiopharmaceutical agent that selectively binds most heavily to bone metastases sites. This study will be the first prospective phase II trial to assess the pain efficacy and anti-tumor activity of Sn-117 m-DTPA in mCRPC with at least one clinically meaningful pain at baseline. Trial registration. ClincialTrials.gov Identifier: NCT04616547.https://doi.org/10.1186/s12885-022-09496-2Metastatic castration resistant prostate cancer with bone metBone painBone seeking radionuclidesPain responseAnalgesic consumptionPatient reported outcome |
| spellingShingle | Zin W. Myint Riham El Khouli Bryan Lemieux Donglin Yan William H. St. Clair Xiaoqi Liu Charles A. Kunos A single arm phase II study of bone-targeted Sn-117 m-DTPA in symptomatic castration-resistant prostate cancer with skeletal metastases BMC Cancer Metastatic castration resistant prostate cancer with bone met Bone pain Bone seeking radionuclides Pain response Analgesic consumption Patient reported outcome |
| title | A single arm phase II study of bone-targeted Sn-117 m-DTPA in symptomatic castration-resistant prostate cancer with skeletal metastases |
| title_full | A single arm phase II study of bone-targeted Sn-117 m-DTPA in symptomatic castration-resistant prostate cancer with skeletal metastases |
| title_fullStr | A single arm phase II study of bone-targeted Sn-117 m-DTPA in symptomatic castration-resistant prostate cancer with skeletal metastases |
| title_full_unstemmed | A single arm phase II study of bone-targeted Sn-117 m-DTPA in symptomatic castration-resistant prostate cancer with skeletal metastases |
| title_short | A single arm phase II study of bone-targeted Sn-117 m-DTPA in symptomatic castration-resistant prostate cancer with skeletal metastases |
| title_sort | single arm phase ii study of bone targeted sn 117 m dtpa in symptomatic castration resistant prostate cancer with skeletal metastases |
| topic | Metastatic castration resistant prostate cancer with bone met Bone pain Bone seeking radionuclides Pain response Analgesic consumption Patient reported outcome |
| url | https://doi.org/10.1186/s12885-022-09496-2 |
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