This phase I trial tests the safety, side effects and best dose of tin (Sn)-177m-diethylenetriaminepentaacetic acid (DTPA) and how well it works in treating prostate, breast or non-small cell lung cancer that has spread from where it first started (primary site) to the bones (bone metastases). Sn-117m-DTPA was originally tested in tumors that had spread to the bones to help reduce bone pain. The drug has been improved and is designed to send low-level radiation to tumors in the bone while being gentler on the bone marrow, where blood cells are made. Sn-117m-DTPA may be safe and tolerable, and may slow down or shrink tumors in patients with metastatic prostate, breast, or non-small cell lung cancer that has spread to the bones.
PRIMARY OBJECTIVE: I. To assess the safety and tolerability of tin Sn 117m pentetate (Sn-117m- diethylenetriaminepentaacetic acid \[DTPA\]) per Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity by prostate-specific membrane antigen (PSMA) positron emission tomography (PET) response criteria for prostate cancer and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) response criteria for breast and non-small cell lung cancers. II. To evaluate time to the first symptomatic skeletal event defined as (i) the first use of external-beam radiation therapy to relieve skeletal symptoms; (ii) new symptomatic pathologic vertebral or nonvertebral bone fractures; (iii) spinal cord compression; or (iv) tumor-related orthopedic surgical intervention (Scher et al., 2016). III. To measure changes and time to progression in serum prostate-specific antigen (PSA) (in prostate cancer patients only), and bone-specific alkaline phosphatase (bALK PHOS) (in all patients). IV. To evaluate 2-year progression-free survival (PFS) and overall survival (OS) rates. V. To characterize the biodistribution and dosimetry of high specific activity Sn-117m-DTPA in the treated population. OUTLINE: This is a dose-escalation study followed by a dose-expansion study. Patients receive Sn-117m-DTPA intravenously (IV) over 10 minutes on day 1 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo urine and blood sample collection, PET/computed tomography (CT) and single photon emission computed tomography (SPECT)/CT throughout the study. Additionally, prostate cancer patients undergo technetium TC-99m (Tc-99m) bone scan at baseline and PSMA PET/CT throughout the study. After completion of study treatment, patients are followed up every 6 months until death.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Undergo urine and blood sample collection
Undergo technetium TC-99m bone scan
Undergo PET/CT, SPECT/CT and PSMA PET/CT
Undergo PET/CT
Undergo PSMA PET/CT
Undergo SPECT/CT
Undergo technetium TC-99m bone scan
Given IV
Frequency of dose-limiting toxicities
Will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Will be summarized by severity grade, system organ class, and their relation to study treatment.
Time frame: Up to completion of 1 cycle (cycle length = 56 days)
Frequency of adverse events
Will be graded using NCI CTCAE v 5.0. Will be summarized by severity grade, system organ class, and their relation to study treatment.
Time frame: Up to 30 days after last dose of study treatment
Tumor response
Will be evaluated using prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) for prostate cancer and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) for breast and non-small cell lung cancers. Categorical endpoints will be summarized by frequency and percent. Continuous variables will be summarized by mean and standard deviation at each assessment time point.
Time frame: Up to 2 years
Time to first symptomatic skeletal event
Will be defined as the first use of external-beam radiation therapy to relieve skeletal symptoms, new symptomatic pathologic vertebral or non-vertebral bone fractures, spinal cord compression or tumor-related orthopedic surgical intervention. Categorical endpoints will be summarized by frequency and percent. Continuous variables will be summarized by mean and standard deviation at each assessment time point. Will be analyzed using the Kaplan-Meier product limit method. Estimation and confidence intervals for the median time to first symptomatic skeletal event will be provided.
Time frame: Up to 2 years
Changes in serum PSA (prostate cancer patients only)
Categorical endpoints will be summarized by frequency and percent. Continuous variables will be summarized by mean and standard deviation at each assessment time point. Will be calculated for each of the above defined categories with the corresponding confidence intervals.
Time frame: At baseline, days 44-56 of cycle 1, and days 30-56 of cycle 2
Time to progression in serum PSA (prostate cancer patients only)
Categorical endpoints will be summarized by frequency and percent. Continuous variables will be summarized by mean and standard deviation at each assessment time point. Will be calculated for each of the above defined categories with the corresponding confidence intervals.
Time frame: At baseline, days 44-56 of cycle 1, and days 30-56 of cycle 2
Changes in bone-specific alkaline phosphatase levels (all patients)
Categorical endpoints will be summarized by frequency and percent. Continuous variables will be summarized by mean and standard deviation at each assessment time point. Will be calculated for each of the above defined categories with the corresponding confidence intervals.
Time frame: At baseline, days 44-56 of cycle 1, and days 30-56 of cycle 2
Progression-free survival
Categorical endpoints will be summarized by frequency and percent. Continuous variables will be summarized by mean and standard deviation at each assessment time point. Will be analyzed using the Kaplan-Meier product limit method.
Time frame: From the first study treatment until the date of PERCIST definition of progression for breast and non-small cell lung cancers and PSMA PET/CT definition of progression for prostate cancer, assessed up to 2 years
Overall survival
Categorical endpoints will be summarized by frequency and percent. Continuous variables will be summarized by mean and standard deviation at each assessment time point. Will be analyzed using the Kaplan-Meier product limit method.
Time frame: From the first study treatment until the date of death, assessed up to 2 years
Biodistribution and dosimetry of high specific activity tin (Sn)-117m-diethylenetriaminepentaacetic acid (DTPA)
Categorical endpoints will be summarized by frequency and percent. Continuous variables will be summarized by mean and standard deviation at each assessment time point. All results are expressed as mean percent of injected dose +/- standard deviation; the mean values will be tested by Student t test for statistical significance. Regions of interest will be drawn over normal bone and metastatic foci, and decay-corrected counts of pixels drawn from all Sn-117m-DTPA scans. Counts per pixels will be plotted against time. Time to peak was noted for both normal and metastatic bone lesions. The slope of the curve will be assessed for evidence of washout.
Time frame: On days 1, 2, 4, and 43 of cycle 1
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