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

NCT06105918 | Active Not Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: STUDY00005677NCI-2023-03480RAD5633-23P30CA138292
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prostate Adenocarcinoma; Biochemically Recurrent Prostate Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Tumor and organ at risk dosimetry

  At 1-3 days and 4-7 days post radioligand therapy

• Circulating tumor deoxyribonucleic acid (ctDNA) differences

  Up to 5 years

• ctDNA differences

  Up to 5 years

• ctDNA differences

  Up to 5 years

Study Arms (1)

Treatment (EBRT, 177Lu-rhPSMA-10.1)

EXPERIMENTAL

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; Procedure: Computed Tomography; Radiation: External Beam Radiation Therapy; Other: Flotufolastat F-18; Drug: Lutetium Lu 177 PSMA-10.1; Procedure: Positron Emission Tomography; Procedure: Single Photon Emission Computed Tomography

Interventions

Computed Tomography PROCEDURE

Undergo rhPSMA-7.3 PET/CT and SPECT-CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (EBRT, 177Lu-rhPSMA-10.1)

External Beam Radiation Therapy RADIATION

Undergo EBRT

Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy, External Beam Radiotherapy (conventional), External Beam RT, external radiation, External Radiation Therapy, external-beam radiation, Radiation, External Beam, Teleradiotherapy, Teletherapy, Teletherapy Radiation

Treatment (EBRT, 177Lu-rhPSMA-10.1)

Flotufolastat F-18 OTHER

Given IV

Also known as: (18F)-rhPSMA-7.3, 18F-rhPSMA-7.3, 18FrhPSMA-7.3, F-18-rhPSMA-7.3, Fluorine F 18 radiohybrid PSMA-7.3, Fluorine F 18 rhPSMA-7.3, Fluorine-18 rhPSMA-7.3, rhPSMA-7.3 (18F)

Treatment (EBRT, 177Lu-rhPSMA-10.1)

Lutetium Lu 177 PSMA-10.1 DRUG

Given IV

Also known as: (177Lu) rhPSMA-10.1, 177Lu Radiohybrid PSMA-10.1, 177Lu rhPSMA-10.1, 177Lu-rhPSMA-10.1

Treatment (EBRT, 177Lu-rhPSMA-10.1)

Positron Emission Tomography PROCEDURE

Undergo rhPSMA-7.3 PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (EBRT, 177Lu-rhPSMA-10.1)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (EBRT, 177Lu-rhPSMA-10.1)

Single Photon Emission Computed Tomography PROCEDURE

Undergo SPECT-CT scan

Also known as: Medical Imaging, Single Photon Emission Computed Tomography, Single Photon Emission Tomography, Single-Photon Emission Computed, single-photon emission computed tomography, SPECT, SPECT imaging, SPECT SCAN, SPET, ST, tomography, emission computed, single photon, Tomography, Emission-Computed, Single-Photon

Treatment (EBRT, 177Lu-rhPSMA-10.1)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Wurzer A, De Rose F, Fischer S, Schwaiger M, Weber W, Nekolla S, Wester HJ, Eiber M, D'Alessandria C. Preclinical comparison of [177Lu]Lu-rhPSMA-10.1 and [177Lu]Lu-rhPSMA-10.2 for endoradiotherapy of prostate cancer: biodistribution and dosimetry studies. EJNMMI Radiopharm Chem. 2024 Feb 26;9(1):18. doi: 10.1186/s41181-024-00246-2.

  PMID: 38407630 DERIVED

MeSH Terms

Interventions

Specimen Handling; Congresses as Topic; Radiation; Lutetium-177; Magnetic Resonance Spectroscopy; X-Rays; Photons

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Organizations; Health Care Economics and Organizations; Physical Phenomena; Spectrum Analysis; Chemistry Techniques, Analytical; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Radiation, Ionizing; Elementary Particles; Light; Optical Phenomena; Radiation, Nonionizing

Study Officials

• David M Schuster, MD, FACR

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 10, 2023
• First Posted: October 30, 2023
• Study Start: November 29, 2023
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2029
• Last Updated: December 9, 2025

Record last verified: 2025-12

Locations

US (1)