Adding 177Lu-PSMA-617 to EBRT and short ADT for high-risk localized prostate cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase 2 trial compares two treatment approaches for high-risk localized prostate cancer: standard external beam radiation therapy with 24 months of androgen deprivation therapy, versus the same EBRT regimen plus 6 months of ADT with the radiopharmaceutical 177Lu-PSMA-617. The aim is to see if the combination can deliver similar or better cancer control while reducing ADT-related toxicity and improving quality of life. Eligible participants have specific high-risk features, confirmed prostate cancer, localized disease, adequate organ function, and PSMA-PET positivity. The study is led by Johns Hopkins, with collaboration from Novartis, and is conducted at a single center in Baltimore, MD.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* 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:

  1. Platelet count of \>100 x109/L
  2. White blood cell (WBC) count \> 3,000/mL
  3. Neutrophil count of \> 1,500/mL
  4. Hemoglobin ≥ 10 g/dL
  5. 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.
  6. Total bilirubin \< 3 x ULN (except if confirmed history of Gilbert's disease)
  7. Serum albumin \> 30 g/L
  8. Aspartate aminotransferase (AST) \< 3 times the ULN
* For male patients with partners of childbearing potential, agreement to use barrier contraceptive method (condom) and to continue its use for 6 months from receiving the last dose of 177Lu-PSMA-617.
* Patient must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* 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.

Where it's running

• Johns Hopkins University
  Baltimore, Maryland, United States Recruiting

Study contacts

• Principal investigator: Ana Kiess — Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Study coordinator: Ana Kiess
• Email: akiess1@jhmi.edu
• Phone: 443-287-7528

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Prospective Prostate Cancer Infrastructure for High-Risk and Metastatic Disease

  This study will collect long-term real-world data and biomaterials from men with high-risk localized or metastatic hormone-sensitive prostate cancer to understand everyday treatment patterns and quality of life.

  Recruiting Radboud University Medical Center · Nijmegen · NCT07560748

• Darolutamide plus hormone therapy before prostate removal for men with high-risk localized prostate cancer

  This study tests whether adding darolutamide to standard hormone (androgen-deprivation) therapy for 12 or 24 weeks before prostate removal helps men with high-risk localized prostate cancer.

  Recruiting at 17 sites Phase 2 Bayer · Hefei, Anhui and 22 other locations · NCT07450599

• Precision radiotherapy guided by molecular MRI (APT imaging)

  This project will test whether a special MRI scan called amide proton transfer (APT) imaging can better identify the most aggressive areas of glioblastoma to guide radiotherapy in adults.

  Recruiting Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Baltimore, Maryland · NCT07512154

• DNAJB1-PRKACA vaccine plus DRP-104, nivolumab, and ipilimumab for advanced fibrolamellar liver cancer

  A early-stage study tests whether a personalized vaccine plus two immune drugs and a glutamine-blocking agent can safely help people with advanced fibrolamellar liver cancer.

  Recruiting Phase 1 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Baltimore, Maryland · NCT07430202

• Ruxolitinib for IEC-HS after CAR-T therapy

  This pilot study tests whether ruxolitinib can help treat IEC-HS that can occur after CAR-T therapy in adults.

  Recruiting Phase 1 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Baltimore, Maryland · NCT07424222

• Music therapy for patients with newly diagnosed GBM after chemoradiation

  This study tests whether adding music therapy helps improve quality of life for adults with newly diagnosed glioblastoma who are receiving standard treatment.

  Recruiting Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Baltimore, Maryland · NCT07375992

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.