ETCTN 10437: A single-arm phase II study of bone-targeted sn-117m-DTPA in symptomatic castration-resistant prostate cancer with skeletal metastases.

TPS5095 Background: Most patients with metastatic castration resistant prostate cancer (mCRPC) develop bone metastases with debilitating pain that is itself associated with shorter survival. Several bone-seeking radionuclides have been developed for palliation of metastatic bone pain. To date, radium-223 dichloride is the first and only approved targeted alpha therapy for mCRPC; the major dose limitation is bone marrow toxicity with modest pain relief. Sn-117m-diethylenetriaminepentaacetic acid (DPTA), is a complex of a radioisotope of tin with DTPA. It emits a low-energy conversion electron and also yields a gamma emission. Sn-117m-DPTA localizes selectively in bone, and the limited range (0.2-0.3 mm) of its conversion electrons resulting in deeper tissue penetration with less radiation effects on bone marrow as compared to radium-223 dichloride. Srivastava et al. (1998) reported in a phase I/II study of patients with painful bone metastases from a variety of solid tumors, 45% of patients obtained reduction of pain by at least 50%, and 30% had complete relief of pain for more than two weeks after one injection. Thus, Sn-117m-DTPA has high palliative efficacy with little significant toxicity. Additional evaluation of this agent in mCRPC patients is urgently required. Methods: The study is a phase 2 single-arm clinical trial of Sn-117m-DPTA (20 mCi/70Kg or 0.28 mCi/kg) intravenously every 8 weeks for two injections for patients with mCRPC metastatic to at least two bone sites with at least one clinically meaningful pain site at baseline. Re-treatment with additional two cycles is allowed if patients meet re-treatment criteria. Key eligibility criteria include 1) refractory mCRPC patients who progressed on any lines of therapies 2) self-reported bone pain (≥4 on an 11-point pain intensity scale), and 3) must be on either regular pain medication or have undergone palliative radiation for bone pain within 12 weeks prior to starting study treatment. Key exclusion criteria include 1) visceral metastases and 2) malignant lymphadenopathy exceeding 3cm in short-axis diameter. Twenty-five patients will be enrolled with a primary objective to assess the efficacy of Sn-117m-DTPA on sustained pain response; defined as 1) achieving pain index ≤3 index within a 12-week period and 2) maintaining pain index ≤3 over a 16-week period. Secondary endpoints include patient reported outcomes, adverse events, progression-free survival and overall survival. Correlative aims include assessing blood (systemic inflammatory markers) and tissue biomarkers (gene sequencing and polo-like kinase-1) for association with clinical benefit. An interim analysis will be performed to assess efficacy after 10 patients become evaluable. The study began enrolling patients in December 2021 and is ongoing. Clinical trial information: NCT04616547.