Radioligand Therapy After PSMA PET Guided External Beam Radiotherapy for Treating Post-Prostatectomy Patients With Biochemically Recurrent Prostate Cancer

Phase 1 Trial to Determine Safety and Feasibility in Treating Biochemical Recurrence Post-Prostatectomy With PSMA PET Guided External Beam Radiotherapy Followed by Consolidative Radioligand Therapy

This phase I trial tests the safety, side effects and best dose of radioligand therapy (lutetium Lu 177 PSMA-10.1 [177Lu-rhPSMA-10.1]) after prostate specific membrane antigen (PSMA) positron emission tomography (PET)-guided external beam radiotherapy in treating post-prostatectomy patients with prostate cancer that has come back after a period of improvement (recurrent). In this study, radioligand therapy is a radioactive drug called 177Lu-rhPSMA-10.1. It works by binding to PSMA-expressing prostate tumor cells and delivering the radioactive portion of the drug directly to the tumor cells while not harming normal cells. Radiation therapy such as external beam radiotherapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radioligand therapy with PSMA PET-guided external beam radiotherapy may kill more tumor cells in post-prostatectomy patients with biochemically recurrent prostate cancer.

Study Overview

• Status: Recruiting
• Conditions: Biochemically Recurrent Prostate Carcinoma; Prostate Adenocarcinoma
• Intervention / Treatment: Procedure: Biospecimen Collection; Radiation: External Beam Radiation Therapy; Procedure: Computed Tomography; Other: Flotufolastat F-18; Drug: Lutetium Lu 177 PSMA-10.1; Procedure: Positron Emission Tomography; Procedure: Single Photon Emission Computed Tomography

Detailed Description

PRIMARY OBJECTIVES:

I. Demonstrate the safety and feasibility of treating radiotherapy (RT) prostate cancer patients via addition of lutetium Lu 177 PSMA-10.1 (177Lu-rhPSMA-10.1) in a selected post-prostatectomy population.

II. Analyze dosimetry of radioligand therapy (RLT) after each cycle of 177Lu-rhPSMA-10.1.

EXPLORATORY OBJECTIVE:

I. Determine the feasibility of and develop preliminary data in the correlation of circulating tumor circulating tumor deoxyribonucleic acid (ctDNA) at baseline, after RT, and RLT.

OUTLINE: This is a dose-escalation study of 177Lu-rhPSMA-10.1.

Patients undergo external beam radiation therapy (EBRT) followed by 177Lu-rhPSMA-10.1 intravenously (IV) on study. Patients also receive flotufolastat F-18 (rhPSMA-7.3) IV with positron emission tomography (PET)/computed tomography (CT) at screening and undergo single-photon emission computed tomography (SPECT)-CT and collection of blood samples on study.

Patients follow up 6 weeks after the last 177Lu-rhPSMA-10.1 administration.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: David M Schuster, MD, FACR; Phone Number: 404-712-4859; Email: dschust@emory.edu
• Study Contact Backup: Name: Ashesh B. Jani, MD, MSEE, FASTRO; Phone Number: 404-778-3473; Email: abjani@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University Hospital/Winship Cancer Institute
      • Contact: David M. Schuster, MD, FACR; Phone Number: 404-712-4859; Email: dschust@emory.edu
      • Contact: Bridget Fielder, RN; Email: bfielde@emory.edu
      • Principal Investigator: David M. Schuster, MD, FACR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adenocarcinoma of the prostate, post radical prostatectomy with detectable prostate specific antigen (PSA)
• Clinical PSMA PET/CT obtained, with findings of pelvic uptake only (prostate bed, pelvic lymph node uptake, or both)
• Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0-2
• Age over 18

Exclusion Criteria:

• Contraindications to radiotherapy (including active inflammatory bowel disease or prior pelvic radiotherapy or prior RLT)
• Risk factors for Lu-rhPSMA radioligand therapy (Baseline >= grade 2 myelosuppression, renal insufficiency [glomerular filtration rate (GFR) < 60 mL/min], or xerostomia)
• Definitive findings of systemic metastasis prior imaging (if obtained) or biopsy (if obtained)
• Unacceptable medical or radiation safety risk
• Unmanageable urinary tract obstruction or hydronephrosis; patients with diagnosed or who are at high risk of urinary retention
• GFR < 60 mL/min or creatinine > 1.5-fold upper limit of normal (ULN)
• Liver enzymes > 5-fold ULN
• Total white cell count less than 2.5 x 10^9 /L
• Platelet count less than 75 x 10^9 /L
• Any baseline grade 2 or above myelosuppression, nephrotoxicity, hepatotoxicity, xerostomia, or gastrointestinal (GI) toxicity

• Severe acute co-morbidity, defined as follows:

  • Unstable angina and/or congestive heart failure requiring hospitalization in the last 3 months
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
  • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immunocompromised patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (EBRT, 177Lu-rhPSMA-10.1); Patients undergo EBRT followed by 177Lu-rhPSMA-10.1 IV on study. Patients also receive rhPSMA-7.3 IV with PET/CT at screening and undergo SPECT-CT and collection of blood samples on study.

Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Radiation: External Beam Radiation Therapy; Undergo EBRT; Other Names: EBRT; Definitive Radiation Therapy; External Beam Radiation; External Beam Radiotherapy; External Beam RT; external radiation; External Radiation Therapy; external-beam radiation; Radiation, External Beam; Teleradiotherapy; Teletherapy; Teletherapy Radiation; External Beam Radiotherapy (conventional); Procedure: Computed Tomography; Undergo rhPSMA-7.3 PET/CT and SPECT-CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Other: Flotufolastat F-18; Given IV; Other Names: 18F-rhPSMA-7.3; rhPSMA-7.3 (18F); (18F)-rhPSMA-7.3; 18FrhPSMA-7.3; F-18-rhPSMA-7.3; Fluorine F 18 radiohybrid PSMA-7.3; Fluorine-18 rhPSMA-7.3; Fluorine F 18 rhPSMA-7.3; Drug: Lutetium Lu 177 PSMA-10.1; Given IV; Other Names: 177Lu-rhPSMA-10.1; (177Lu) rhPSMA-10.1; 177Lu Radiohybrid PSMA-10.1; 177Lu rhPSMA-10.1; Procedure: Positron Emission Tomography; Undergo rhPSMA-7.3 PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Procedure: Single Photon Emission Computed Tomography; Undergo SPECT-CT scan; Other Names: ST; Medical Imaging, Single Photon Emission Computed Tomography; Single Photon Emission Tomography; single-photon emission computed tomography; SPECT; SPECT imaging; SPECT SCAN; SPET; tomography, emission computed, single photon; Tomography, Emission-Computed, Single-Photon; Single-Photon Emission Computed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of radiotherapy and radioligand therapy related adverse events	Will be summarized descriptively using frequencies and percentages of all captured toxicities by grade and relevance.	Up to 6 weeks post last radioligand therapy dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor and organ at risk dosimetry	Descriptive statistics will be used to perform the post-hoc dosimetry for tumor as applicable and background organs after each cycle of radioligand therapy.	At 1-3 days and 4-7 days post radioligand therapy
Circulating tumor deoxyribonucleic acid (ctDNA) differences	Descriptive statistics (number of subject, mean, median, standard deviation, minimum, and maximum) will be used to summarize baseline ctDNA and post-radiotherapy ctDNA. Wilcoxon Signed-Ranks Test or paired samples t-test will be used to perform comparisons.	Up to 5 years
ctDNA differences	Descriptive statistics (number of subject, mean, median, standard deviation, minimum, and maximum) will be used to summarize post radiotherapy ctDNA and post-radioligand therapy ctDNA. Wilcoxon Signed-Ranks Test or paired samples t-test will be used to perform comparisons.	Up to 5 years
ctDNA differences	Descriptive statistics (number of subject, mean, median, standard deviation, minimum, and maximum) will be used to summarize baseline ctDNA and post-radioligand therapy ctDNA. Wilcoxon Signed-Ranks Test or paired samples t-test will be used to perform comparisons.	Up to 5 years

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: David M Schuster, MD, FACR, Emory University Hospital/Winship Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2023
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: October 10, 2023
• First Submitted That Met QC Criteria: October 25, 2023
• First Posted (Actual): October 30, 2023

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Adenocarcinoma; Physiological Effects of Drugs; Protective Agents; Cariostatic Agents; Fluorides
• Other Study ID Numbers: STUDY00005677 (Other Identifier: Emory University Hospital/Winship Cancer Institute); P30CA138292 (U.S. NIH Grant/Contract); NCI-2023-03480 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); RAD5633-23 (Other Identifier: Emory University Hospital/Winship Cancer Institute)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No