Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Carcinoma

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Bone Density Conservation Agents

All Drugs and Chemicals

Antineoplastic Agents

Diphosphonates

Methylene diphosphonate

Radium Ra 223 dichloride

Technetium Tc 99m Medronate

Radiopharmaceuticals

Patients undergo NaF PET/CT or MDP scan within 45 days prior to cycle 1 day 1. Patients then receive standard of care Ra-223 IV on day 1 of each cycle. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo PSMA PET/CT over 45-60 minutes between 30-60 days after the last dose of Ra-223. Patients also undergo collection of blood samples during screening, on day 1 of every Ra-223 cycle, and at 30 days after the last dose of Ra-223. Patients may also undergo NaF PET/CT or MDP scans during Ra-223 treatment as clinically indicated, and/or CT scans during screening and Ra-223 treatment as clinically indicated.

Radium-223

PSMA Positron Emission Tomography (PET) Scan

Technetium Tc 99M Medronate

Maya Aslam

Thomas A Hope, MD

This phase II trial studies how well prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scans (in combination with bone scans) work in selecting patients for Ra-223 radiation therapy that have castration-resistant prostate cancer that has spread from where it first started (primary site) to the bones (bone metastasis). Ra-223 is a type of therapy that emits radiation. Radiation gives off energy which can kill tumor cells and other cells that may support the tumor cells. Ra-223 is given by infusion into the veins, where it is absorbed by the bones. PSMA PET is a type of scan used to detect prostate cancer tumors. PSMA is a radioactive tracer that binds to a specific protein that is found on prostate tumor cells. The PSMA tracer shows the areas on the PET scan where tumor cells are active. A PET scan uses a special camera to detect the energy given off from radioactive tracers (such as PSMA) to make detailed pictures of areas where the tracer accumulates in the body. The PET scan is often combined with a magnetic resonance imaging (MRI) or computed tomography (CT) scan, which helps to map the locations where PSMA has accumulated. PSMA PET scans may be able to select patients that will benefit the most from Ra-223 treatment.

PRIMARY OBJECTIVE:

I. To determine the PSA50 response rate of participants treated with radium Ra 223 dichloride (Ra-223).

SECONDARY OBJECTIVES:

I. To determine the median overall survival (mOS) of participants treated with Ra-223.

II. To determine the PSA30 response rate of partoicipants treated with Ra-223. III. To determine the time to the first skeletal symptomatic event. IV. To characterize the safety profile of Ra-223 treatment. V. To compare the lesion based PSMA PET response based on sodium fluoride (NaF) PET/technetium Tc-99m medronate (MDP) single photon emission computed tomography (SPECT) uptake.

EXPLORATORY OBJECTIVES; I. To compare the PSA response stratified by PSMA PET tumor volume. II. To determine the location of progression by location. III. Safety on subsequent treatment with PSMA radioligand therapy (RLT).

OUTLINE:

Participants undergo NaF PET/CT or MDP scan within 45 days prior to standard of care (SOC) Ra-223 intravenously (IV). Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Participants then undergo a PSMA PET/CT between 30-60 days after the last dose of Ra-223. Participants also undergo collection of blood samples during screening, on the first day of every Ra-223 cycle, and at 30 days after the last dose. Participants may also undergo a NaF PET/CT or MDP scan during treatment as clinically indicated, and/or CT scans during screening and treatment as clinically indicated.

After completion of Ra-223 treatment, participants are followed up at 30 days, and then every 3-6 months.

Efficacy of Ra-223 in PSMA PET Optimally Selected Patients

The proportion of patients who achieve a greater than 50% decline from baseline prostate specific antigen (PSA) (PSA50) drawn prior to C1D1, at any point in the treatment course, will be descriptively reported along with 95% binomial confidence interval. It will be compared with the historical control by binomial test. A confirmation repeat PSA will be drawn after the initial PSA50 response to confirm the result. A PSA50 will only be counted if two PSA showing a 50% decline are measured.

The proportion of patients who achieve a greater than 30% decline from baseline PSA (PSA30) drawn prior to cycle 1 day 1 (C1D1), at any point in the treatment course, will be descriptively reported along with 95% binomial confidence interval. It will be compared with the historical control by binomial test.

Overall survival The time to event will be defined by the duration from the first date of study therapy to date of death from any cause. We will estimate the survival function using the Kaplan-Meier method, and obtain its 95% confidence bands over the survival times. The median overall survival time and 95% confidence interval of it will be derived from the estimated survival functions.

The time to the first skeletal symptomatic event will measure the time to the first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, or requirement for radiation therapy to relieve bone pain, whichever occurs first. We will also estimate the survival function using the Kaplan-Meier method, and obtain its 95% confidence bands over the survival times. The median survival time and 95% confidence interval of it will be derived from the estimated survival functions.

The incidence and severity of adverse events related to study treatment will be descriptively reported using CTCAE v5.0.

Up to five lesions per patient will be measured by a board certified nuclear medicine physician. For each lesion the maximum SUV (SUVmax) will be measured on PSMA PET and NaF PET. Additionally, the SUVmax on the end of study PSMA PET will also be measured. As there is an underestimation of uptake on MDP bone scan compared to PET, we will multiply the uptake measured on MDP SPECT by 2.3 to correct for the differences in recovery coefficients between the two imaging technologies based on prior comparisons. The percent change in the PSMA PET uptake between baseline and end of study will be measured. A Spearman's rank correlation will be used to compare the baseline NaF uptake for each lesion with the percent change of PSMA PET SUVmax.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy of Ra-223 in PSMA PET Optimally Selected Patients	NCT05924672	Castration-Resi... Metastatic Mali... Stage IVB Prost...	Radium-223 PSMA Positron E... Technetium Tc 9...	18 Years -	University of California, San Francisco
Efficacy of Ra-223 in PSMA PET Optimally Selected Patients	NCT05924672	Castration-Resi... Metastatic Mali... Stage IVB Prost...	Radium-223 PSMA Positron E... Technetium Tc 9...	18 Years -	University of California, San Francisco
Efficacy of Ra-223 in PSMA PET Optimally Selected Patients	NCT05924672	Castration-Resi... Metastatic Mali... Stage IVB Prost...	Radium-223 PSMA Positron E... Technetium Tc 9...	18 Years -	University of California, San Francisco

Spots Global Cancer Trial Database for technetium tc 99m medronate