Recruiting
Phase 1
Phase 2

SBRT & 177Lu PSMA

Sponsor:

Angela Y. Jia, MD PhD

Code:

NCT06574880

Conditions

Malignant Neoplasm of Prostate

Locally Advanced Prostate Cancer

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Lu-PSMA-617

5-fraction Stereotactic Body Radiation Therapy (SBRT)

Study Details

Brief summary:

The goal of this clinical trial is to is to investigate if it is possible to lower the chance of cancer reoccurrence and also preserve quality of life by using the drug Pluvicto instead of androgen-deprivation therapy to the usual radiation therapy for advanced local prostate cancer.

Participants will receive one dose of Pluvicto, followed by radiation about 6 weeks later. Radiation therapy will be completed in 5 treatments over the period of 2 weeks. A second dose of Pluvicto will be given 6 weeks after radiation is complete. Some participants may also receive a third dose of Pluvicto, and this would be given 6 weeks after the second dose of Pluvicto.

Conditions

Malignant Neoplasm of Prostate

Locally Advanced Prostate Cancer

Study ID

NCT06574880

Start date

May 13, 2025

Status verified date

Apr, 2026

Completion date

Mar 1, 2027

Anticipated

Primary completion date

Sep 1, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Participant must be ≥ 18 years of age.
  • ECOG performance status ≤ 1
  • Histologic confirmation of prostate adenocarcinoma of the prostate
  • PSMA avid disease on PSMA PET/CT, where the tumor in the prostate has SUVmax ≥ 10.

  • PSMA PET/CT must be obtained within 4 months.
  • Need ≥ 1 criteria:

  • Node positive disease on PSMA PET/CT or conventional imaging, as defined by having any of the following:

  • Pelvic nodal disease (cN1) as defined by LN stations that commence at the bifurcation of the common iliac vessels
  • Regional nodal disease (M1a) as defined by LN stations that commence at the bifurcation of the aorta and bifurcation of the proximal inferior vena cava to the common iliac veins.
  • In the absence of nodal metastasis, must have ≥ 2 of the following

  • i. cT3a or cT3b by conventional imaging (MRI) or PSMA PET/CT
  • ii. Grade group ≥ 4
  • iii. PSA ≥ 40 ng/mL
  • Adequate organ and marrow function to receive treatment:

  • Hemoglobin > 10 g/dL
  • White blood cell (WBC) > 3000 / mL
  • Absolute neutrophil count ≥ 1,500 / mcL
  • Platelets ≥ 100,000 / mcL
  • Creatinine ≤ 1.5x ULN
  • Estimated glomerular filtration rate (eGFR)\* > 50 mL/min
  • Total bilirubin\*\* < 2× ULN
  • Albumin > 3 g/dL
  • Aspartate aminotransferase (AST) < 3× ULN

  • \*based upon Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation. Participants with estimated GFR between 50 - 60 mL/min will require a 99mTc-TPA GFR test and only participants with non-obstructive pathology will be included in the study.
  • \*\* Total bilirubin ≤ 2x ULN (except for participants with known Gilbert's Syndrome ≤ 3x ULN is permitted)
  • International Prostate Symptoms Score (IPSS) ≤ 15.
  • Medically fit for treatment and agreeable to follow-up.
  • Ability to understand and the willingness to sign a written informed consent.
  • Participants with partners of childbearing potential, agreement to use barrier contraceptive method (condom) and to continue its use for 14 weeks from receiving the last dose of Lu-PSMA-617. Participants must also not donate sperm for 14 weeks from receiving the last dose of Lu-PSMA-617.

Exclusion Criteria:

  • Clinical or radiographic evidence of distant metastatic disease (M1a above aortic bifurcation, M1b, or M1c) by any imaging. Participants are allowed to M1a nodal disease that is below the aortic bifurcation. Negative PSMA PET/CT is an acceptable substitute to conventional staging.
  • Prostate gland size >90 cc measured by CT, ultrasound, or MRI
  • Prior head and neck radiation therapy.
  • Prior treatment for prostate cancer (incudes chemotherapy, radiation therapy, or anti-androgen therapy).
  • Prohibited within 30 days prior to administration to study treatment: spironolactone and other investigational drug therapies.
  • Prohibited 3 months before participant registration and during administration of study treatment: oral ketoconazole, , estrogens, and radiopharmaceuticals.
  • History of prior pelvic radiation therapy.
  • Enrollment concurrently in another investigational drug study within 6 months of registration.
  • History of another active malignancy within the previous 3 years except for adequately treated skin cancer or superficial bladder cancer.
  • History of prior myelodysplastic syndrome or acute leukemia.
  • History of or active Crohn's disease or ulcerative colitis.
  • Contraindication to or inability to tolerate PSMA/PET.
  • Any condition that in the opinion of the investigator would preclude participation in this study.
  • Inability to adhere to radiation safety measures in hospital or at home
  • Prior treatment with radionuclide therapies, 177Lu-PSMA-617 or other
  • Reduced salivary gland function with baseline CTCAE Gr > 1 dry mouth will be excluded.

Study Design

Enrollment

45 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Lu-PSMA-617 + SBRT

  • Lu-PSMA-617: 7.4GBq intravenous infusion once with cycle 1, followed by 7.4GBq cycle 2 that is delivered 6 weeks after SBRT , and potentially 7.4GBq cycle #3 delivered 6 weeks after cycle #2 pending dose escalation
  • Radiation therapy: 5 fractions to prostate and elective nodal irradiation, SBRT, delivered 6 weeks after cycle 1 of 177Lu-PSMA-617

Interventions

Lu-PSMA-617

Lu-PSMA will be administered at a fixed dose of 7.4GBq per cycle, on a dose escalation schedule:

  • Level 0: Lu-PSMA-617 for 1 cycle, followed 6 weeks later by SBRT.
  • Level 1 (Starting Dose Level): Lu-PSMA-617 for 1 cycle, followed 6 weeks later by SBRT, followed 6 weeks later by cycle 2.
  • Level 2: Lu-PSMA-617 for 1 cycle, followed 6 weeks later by SBRT, followed 6 weeks later by cycle 2, followed 6 weeks later by cycle 3.

5-fraction Stereotactic Body Radiation Therapy (SBRT)

Prostate and nodal SBRT will begin at the completion of cycle 1 (6 weeks after the first Lu-PSMA-617 infusion, ± 4 weeks).

Primary outcome measure

  • Phase I: Maximum tolerated dose (MTD) of Lu-PSMA-617 [ Time Frame: 4 weeks after final dose of treatment (treatment expected to last up to six months) ]
  • Phase II: Androgen deprivation therapy (ADT)-free survival [ Time Frame: 3 years post treatment ]

Central Contacts and Locations

Central contacts

Angela Y Jia, MD, PhD

216-844-3262Angela.Jia@UHhospitals.org

Locations

University Hospitals Cleveland Medical Center Seidman Cancer Center, Case Comprehensive Cancer Center

Recruiting

Cleveland, Ohio, United States, 44106

More Information

Sponsor

Angela Y. Jia, MD PhD

Last update posted

May 26, 2026

Last verified

Apr, 2026

Keywords

  • Prostate cancer

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Angela Y. Jia, MD PhD on 2026-05-26.