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High-Risk Localized Prostate CancerPhase 2NCT07550517

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

A Phase 2 study testing EBRT + 6 mo ADT + 177Lu-PSMA-617 and EBRT + 24 mo ADT in people with High-Risk Localized Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
High-Risk Localized Prostate Cancer
What is being tested?
EBRT + 6 mo ADT + 177Lu-PSMA-617 and EBRT + 24 mo ADT
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteUnited States
Study dates
17 Aug 2026to Aug 2033
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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)
  • Serum albumin > 30 g/L
  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ana Kiess contact

443-287-7528

akiess1@jhmi.edu

Ryan Manuel contact

410-955-4261

rmanuel5@jhmi.edu

United States1 site, 1 recruiting

  • Johns Hopkins University

    Baltimore, Maryland, 21287

    Recruiting

Other trials in United States

About this study

Official title: A Phase II Non-blinded Randomized Study Comparing External Beam Radiotherapy (EBRT), 177Lu-PSMA-617, and Short Term Androgen Deprivation Therapy (ADT) Versus EBRT and Long Term ADT in Men With High Risk Localized Prostate Cancer

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.

Read the detailed description

Men with high-risk localized prostate cancer include those with stage cT3a or Grade Group 4/5 or Prostate Specific Antigen (PSA) >20 ng/mL, and the proportional rate of high-risk disease has increased to 20% of newly diagnosed patients in the US. These patients are currently recommended treatment with a combination of definitive radiotherapy and long-term androgen deprivation therapy (NCCN category 1) or radical prostatectomy with pelvic lymph node dissection. Radiotherapy most often consists of external-beam radiotherapy (EBRT) in 28 to 45 daily fractions with 1.5 to 3 years of ADT. Multiple phase III studies have shown a benefit in survival with long-term ADT. However, given the toxicities of long-term ADT, including fatigue, mood changes, sexual dysfunction, osteopenia, weight gain, diabetes and cardiovascular disease, many patients are reluctant to complete long-term ADT. This leads to significant demand for investigation of lower-toxicity alternatives to long-term ADT for patients with high-risk localized prostate cancer.

The combination of 177Lu-PSMA-617 with definitive EBRT and 6 months ADT for high-risk prostate cancer has the potential to increase the cumulative absorbed dose to the prostate, involved nodes, and micrometastatic disease, as well as decrease toxicity and improve QoL compared with EBRT and long-term ADT. ADT has been shown to increase radiosensitivity and PSMA expression of prostate cancer; therefore 6 months of ADT was selected to optimize the combination therapy while avoiding toxicities associated with long-term ADT. There are significant unknowns with respect to absorbed dose and toxicities of this potential combination of 177Lu-PSMA-617 and EBRT. In addition, the relative efficacy compared to EBRT plus long-term ADT is unknown. The investigators therefore propose a phase II randomized study of dosimetry, safety, and efficacy of Lu-177-PSMA-617, EBRT, and short-term ADT (6 months) in comparison with EBRT and long-term ADT (24 months).

Being tested
EBRT + 6 mo ADT + 177Lu-PSMA-617, EBRT + 24 mo ADT

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    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.

  • EBRT + 24 mo ADTRadiation

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

Study groups in NCT07550517
Study groupRoleWhat they receive
Arm A (EBRT + 6 mo ADT + 177Lu-PSMA-617)ExperimentalParticipants will receive EBRT + 6 mo ADT + 177Lu-PSMA-617
Receives: Drug: EBRT + 6 mo ADT + 177Lu-PSMA-617
Arm B (EBRT + 24 mo ADT)Active comparatorParticipants will receive EBRT + 24 mo ADT
Receives: Radiation: EBRT + 24 mo ADT

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Post randomization up to 3 years.

Secondary outcomes (10)

  1. Biochemical disease-free survival (BC-DFS)

    Measured from randomization to the time of a measured PSA value at least 2 ng/mL above nadir, and at least 25% above nadir, or death, whichever occurs first.

    Measured: From randomization up to 3 years.

  2. Time-to-Next-Intervention (TTNI)

    TTNI is defined as the period of time from randomization to the initiation of any additional cancer-directed therapy. In the absence of a defining event, TTNI will be censored at the date of last visit documenting absence of interventions.

    Measured: From randomization up to 3 years.

  3. ADT-free survival (ADT-FS)

    ADT-free survival defined as the time from randomization to the time of initiation of palliative ADT or death, whichever occurs first.

    Measured: From randomization up to 3 years.

  4. Metastasis-free survival (MFS)

    MFS is defined as the time from randomization to the time of detection of at least one new metastatic lesions on conventional imaging. Patients who do not develop at least one new metastasis will be censored at the time of the last disease assessment.

    Measured: From randomization up to 3 years.

  5. Overall Survival (OS)

    For subjects who do not die, time to death will be censored at the time of last contact.

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

  6. Toxicity as assessed by adverse events

    Toxicity of combination therapy with EBRT + 6 mo ADT + 177Lu-PSMA-617 by collecting CTCAE v5.0 adverse events.

    Measured: In Arm A, AEs assessed 7-10 days prior to every cycle of 177Lu-PSMA-617. In Arm B, AEs assessed at baseline, Day 1, EOT, and after the completion of EBRT. For both arms, starting at 6 months, AEs assessed every 6 months up to 5 years (no Month 54 f/u).

  7. Quality of Life as assessed by Expanded Prostate Index Composite (EPIC)

    Score range, 0-100. Higher score better quality of life.

    Measured: Pre-treatment, end of RT, 6 months, and every 6 months thereafter up to 5 years (no Month 54 f/u).

  8. Quality of Life as assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30

    Score range from 0 to 100. A higher score indicates better quality of life.

    Measured: Pre-treatment, end of RT, 6 months, and every 6 months thereafter up to 5 years (no Month 54 f/u).

  9. Quality of Life as assessed by Xerostomia Quality of Life Scale (XeQoLS)

    Score range 0 to 60, with higher scores indicating worse quality of life.

    Measured: Pre-treatment, end of RT, 6 months, and every 6 months thereafter up to 5 years (no Month 54 f/u).

  10. Correlation of Toxicities and Absorbed Dose

    To correlate rate of CTCAE v5.0 grade 3 toxicities with mean absorbed dose to normal organs at risk. Specifically, pelvic organ toxicities will be correlated with mean EBRT dose, mean Lu-PSMA absorbed dose and mean cumulative absorbed dose for the bladder, rectum, and bowel.

    Measured: In Arm A, AEs assessed 7-10 days prior to every cycle of 177Lu-PSMA-617. In Arm B, AEs assessed at baseline, Day 1, EOT, and after the completion of EBRT. For both arms, starting at 6 months, AEs assessed every 6 months up to 5 years (no Month 54 f/u).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Apr 2026
  2. Study start17 Aug 2026
  3. Primary completionAug 2032 (estimated)
  4. Study completionAug 2033 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07550517
Sponsor's protocol ID
J25104
Other IDs
IRB00494892
Status last verified
Sep 2026
First submitted
7 Apr 2026
Last updated
22 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing EBRT + 6 mo ADT + 177Lu-PSMA-617 and EBRT + 24 mo ADT in people with High-Risk Localized Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ana Kiess (443-287-7528, akiess1@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of testosterone recovery (TR) (time frame: Post randomization up to 3 years.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07550517.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026.

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