PSMA-High: EBRT/ PSMA617/ ADT vs. EBRT/ ADT

NCT07550517 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: J25104IRB00494892
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This research is being done to find out if the study drug, 177Lu-PSMA-617, given before and during standard of care External Beam Radiation Therapy (EBRT) treatment, with a shorter course of Androgen Deprivation Therapy (ADT) (6 months) is (1) safe and effective compared to standard of care alone, and (2) can reduce the side effects caused by long-term (24 months) ADT in men with high risk localized prostate cancer.

Conditions

High-Risk Localized Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Rate of testosterone recovery (TR)

  The rate of testosterone recovery (TR) will be determined by the percentage of patients who recover normal T levels within 3 years after randomization.

  Post randomization up to 3 years.

Secondary Outcomes (10)

• Biochemical disease-free survival (BC-DFS)

  From randomization up to 3 years.

• Time-to-Next-Intervention (TTNI)

  From randomization up to 3 years.

• ADT-free survival (ADT-FS)

  From randomization up to 3 years.

• Metastasis-free survival (MFS)

  From randomization up to 3 years.

• Overall Survival (OS)

  From randomization to the date of death, up to 3 years.

Study Arms (2)

Arm A (EBRT + 6 mo ADT + 177Lu-PSMA-617)

EXPERIMENTAL

Participants will receive EBRT + 6 mo ADT + 177Lu-PSMA-617

Drug: EBRT + 6 mo ADT + 177Lu-PSMA-617

Arm B (EBRT + 24 mo ADT)

ACTIVE COMPARATOR

Participants will receive EBRT + 24 mo ADT

Radiation: EBRT + 24 mo ADT

Interventions

EBRT + 6 mo ADT + 177Lu-PSMA-617 DRUG

In Arm A, 177Lu-PSMA-617 will be given as intravenous infusion every 6 weeks, up to 4 cycles. Cycle 1 Day 1 (C1D1) of 177Lu-PSMA-617 will start at least 2 weeks after ADT, and EBRT will start at least 2 weeks after C1D1.

Arm A (EBRT + 6 mo ADT + 177Lu-PSMA-617)

EBRT + 24 mo ADT RADIATION

In Arm B, EBRT will start 3-7 weeks after Day 1 of ADT.

Arm B (EBRT + 24 mo ADT)

Eligibility Criteria

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

You may qualify if:

• Patient must have high-risk prostate cancer (HRPC) defined by presence of exactly one high-risk feature: cT3a OR Grade Group 4 or 5 OR PSA \> 20 ng/mL.
• Histologic confirmation of adenocarcinoma of the prostate.
• Patient must have localized HRPC defined by conventional imaging (no N1 disease by CT or MRI). Patients with or without intra-pelvic nodal metastases by PSMA-PET may be included as long as not enlarged \>10mm short axis by conventional CT size criteria.
• Patients must have PSMA-PET (68Ga-PSMA-11 or 18F-DCFPyL) with prostate tumor SUVmax \> 10.
• Patient must qualify for definitive treatment of prostate cancer including EBRT as well as ADT (up to 45 days of prior ADT is allotted).
• Patient must be ≥ 18 years of age.
• Patient must have a life expectancy ≥ 24 months.
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Adequate bone marrow reserve and organ function as demonstrated by complete blood count and chemistry panel completed within the prior 6 weeks demonstrating:
• Platelet count of \>100 x109/L
• White blood cell (WBC) count \> 3,000/mL
• Neutrophil count of \> 1,500/mL
• Hemoglobin ≥ 10 g/dL
• Estimated glomerular filtration rate (eGFR) \> 50 mL/min based upon Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Due to safety concerns relating to renal clearance and toxicity of 177Lu-PSMA-617, patients with estimated GFR between 50 - 60 mL/min will require a 99mTc-TPA GFR test and only patients with non-obstructive pathology will be included in the study.
• Total bilirubin \< 3 x ULN (except if confirmed history of Gilbert's disease)

You may not qualify if:

• Presence of a very high-risk feature: cT3b to T4 OR primary pattern 5 OR 2 to 3 high-risk features OR \>4 cores with Grade Group 4 or 5.
• Any prior pharmacotherapy (with the exception of up to 45 days of ADT prior to randomization), radiation therapy, or surgery as treatment for prostate cancer. Any prior radiopharmaceutical therapy.
• Any prior radiation to the pelvis.
• Presence of N1 or M1 disease by conventional imaging (CT, MRI, and/or bone scan) or M1 disease by PSMA-PET (68Ga-PSMA-11 or 18F-DCFPyL). Lymph nodes with short axis \> 8 mm by CT will be considered N1 by conventional imaging.
• Castration-resistant prostate cancer (CRPC).
• Patient receiving any other investigational agents.
• Patient is participating in a concurrent treatment protocol involving radiotherapy, surgery, or systemic anti-cancer agents.
• Inadequate bone marrow reserve and organ function as detailed in 5.1.10.
• Unable to lie flat during or tolerate PET/MRI, PET/CT or EBRT.
• Concurrent serious medical condition that, in the opinion of the Investigator, would impair study participation.
• Contraindication to receiving pelvic radiation, including history of or active inflammatory bowel disorders.
• Refusal to sign informed consent.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Interventions

Pluvicto

Study Officials

• Ana Kiess

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ana Kiess

CONTACT

443-287-7528; akiess1@jhmi.edu

Ryan Manuel

CONTACT

410-955-4261; rmanuel5@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2026
• First Posted: April 24, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): July 1, 2032
• Study Completion (Estimated): July 1, 2033
• Last Updated: June 24, 2026

Record last verified: 2026-06

Locations

US (1)