Prostate Cancer Clinical Trial
Treatment of Cancer-Related Bone Pain by Using Bone-Targeted Radiation-Based Therapy (Sn-117m-DTPA) in Patients With Prostate Cancer That Has Spread to Bones
This phase II trial studies the effect of Sn-117m-DTPA on bone pain in patients with prostate cancer that has spread to the bones. Sn-117m-DTPA is a radioactive therapeutic agent that localizes to bones when given to patients. Sn-117m-DTPA may help reduce bone pain in patients with prostate cancer that has spread to the bones.
I. To evaluate the efficacy of tin-117m diethylenetriaminepentaacetic acid (Sn-117m-DTPA) on sustained pain response in patients with castration-resistant prostate cancer (CRPC) metastatic to at least two bone sites with at least one clinically meaningful pain at baseline (>= 4 on an 11-point pain intensity scale).
I. To assess the safety and tolerability of Sn-117m-DTPA per Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
II. To measure Sn-117m-DTPA activity by gamma-camera dosimetry scans (serial full body planar images) obtained at 1 hour, 4 hours (or within 4-6 hours), 24 hours (or within 16-24 hours), 48 hours (or within 36-48 hours), 72 hours (or within 60-72 hours), 1 week (+/- 2 days), and 4 weeks (+/- 2 days) after the first Sn-117m-DTPA administration.
III. To evaluate the therapeutic efficacy of Sn-117m-DTPA at 24 weeks as measured by Prostate Cancer Working Group 3 (PCWG3) criteria.
IV. 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.
V. To evaluate the overall pain response rate at 24 weeks. VI. To evaluate the duration of pain response defined as from the time of improvement in pain response (pain index =< 3) until the pain recurs.
VII. To measure changes and time to progression in serum prostate-specific antigen (PSA) and serum alkaline phosphatase (ALP) levels.
VIII. To measure patient-reported outcomes (PROs) and adverse events (AEs) (PRO-CTCAE) captured by digital instruments.
IX. To evaluate progression-free survival (PFS) and overall survival (OS).
I. To examine any tumor genomic alterations that may be associated with response or resistance to Sn-117m-DTPA, a radiopharmaceutical agent.
II. To examine the changes in systemic inflammatory markers (such as interferon [IFN]-gamma, tumor necrosis factor [TNF]-alpha, interleukins [IL]-8, IL-10, and IL-17) by flow cytometry, and changes in markers of immune function by measuring the percentage and absolute number of CD4+ T helper cells, CD8+ T cytotoxic cells, T regulatory cells, polymorphonuclear (PMN) myeloid-derived suppressor cells (MDSCs), and mononuclear MDSCs (M-MDSCs) prior to treatment versus (vs.) end of cycle 1, end of cycle 2, and at week 24 and correlate values and/or changes with treatment outcomes.
III. To evaluate the feasibility of measuring polo-like kinase 1 (Plk1) expression via immunohistochemistry (IHC) staining on archival tissues.
Patients receive tin Sn 117m DTPA intravenously (IV) over 5-10 minutes on day 1. Treatment repeats every 8 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive tin Sn 117m DTPA for an additional 2 cycles if pain recurs within 6 months after a 16-week pain observation period and no disease progression on bone scans, or evidence of clinical progression.
After completion of study, patients are followed up every 4 weeks until week 28, and then every 3 months for up to 12 months after the first dose of tin Sn 117m DTPA.
Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate that is castration-resistant, defined as:
A castrate serum testosterone level =< 50 ng/dL or 1.7 nmol/L
Bilateral orchiectomy or maintenance on androgen ablation therapy with luteinizing hormone-releasing hormone (LHRH). Androgen deprivation therapy needs to be maintained throughout the study unless a patient has had orchiectomy by surgery
Serum PSA progression defined as two consecutive increases in PSA over a previous reference value, each measurement at least 1 week apart
Progression after androgen receptor blockers (enzalutamide, apalutamide, or darolutamide) or androgen synthesis blockers (abiraterone acetate) or chemotherapy (docetaxel or cabazitaxel). There are no maximum number of prior therapies
Progressive castration-resistant prostate cancer with two or more skeletal metastases identified by Tc-99m bone scintigraphy or prostate specific membrane antigen (PSMA) positron emission tomography (PET) scan
Patients must have self-reported moderate to severe pain at trial entry (baseline weekly average "worst pain in the past 24-hours" scores of >= 4 on an 11-point numeric rating scale [NRS], the Brief Pain Inventory - Short Form [BPI-SF] item #3 for worst pain)
Patients must either currently employ regular (not occasional) analgesic medication use for cancer-related bone pain or have undergone treatment with external beam radiation therapy (EBRT) for bone pain within 4 weeks before starting study treatment
Age >= 18 years. Children < 18 years of age are excluded from the study as the prevalence of prostate cancer is extremely rare in this age group
Patients must have a life expectancy >= 3 months
Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
Patients must have a serum PSA value >= 1 ng/mL
Absolute neutrophil count >= 1,000/mcL
Platelets >= 100,000/mcL
Hemoglobin > 10.0 g/dL
Total bilirubin =< 2.5 x institutional upper limit of normal (ULN)
Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) =< 5 x institutional ULN
Creatinine =< 1.7 mg/dL OR glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2
Patients receiving bisphosphonates prior to enrollment can maintain bisphosphonate therapy throughout all or part of the study. The bisphosphonate may be stopped or started at the discretion of the investigator throughout the study (i.e., both treatment phase and follow-up). Injection of bisphosphonates should be done at least 2 hours before or after study drug administration
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class 2B or better
The effects of Sn-117m-DTPA on the developing human fetus are unknown. For this reason and because radionuclides are known to be teratogenic, male participants and their female partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while her male partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of Sn-117m-DTPA administration
Patients must be willing and able to comply with the protocol and agree to return to the hospital for follow-up visits and examinations
Ability to understand and the willingness to sign a written informed consent document
Patients must not have visceral metastases (such as liver and lung) as assessed by abdominal/pelvic computed tomography (CT) or chest X-ray within 12 weeks before starting study treatment
Patients must not have malignant lymphadenopathy exceeding 3 cm in short-axis diameter
Patients must not have imminent or established spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI)
Patients who have had chemotherapy, immunotherapy, or external radiotherapy within 4 weeks prior to entering the study
Patients must not have received systemic radiotherapy with radium-223, strontium-89, samarium-153, rhenium-186, or rhenium-188 for the treatment of bony metastases within 24 weeks before starting study treatment
Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
Patients must not have received any investigational agents within 4 weeks before starting study treatment, nor be scheduled to receive one during the planned treatment period
Patients must not have unmanageable urinary incontinence
Patients must not have had known non-pathological bone fractures within 2 months before starting study treatment
Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Sn-117m-DTPA
Patients must not have uncontrolled intercurrent illness, including:
Any uncontrolled infection
Grade 2 or greater motor or sensory neuropathy
Crohn's disease or ulcerative colitis
Patients with psychiatric illness/social situations that would limit compliance with study requirements
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There is 1 Location for this study
Lexington Kentucky, 40536, United States
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