Neoadjuvant Lu-177-PSMA-617 in Patients With High Risk Localized Prostate Cancer Undergoing Radical Prostatectomy

March 20, 2026 updated by: Hackensack Meridian Health

Phase II Study of Neoadjuvant Lu-177-PSMA-617 in Patients With High Risk Localized Prostate Cancer Undergoing Radical Prostatectomy

Male adults with a confirmed diagnosis of prostate adenocarcinoma who meet criteria for localized high risk prostate cancer according to the NCCN guidelines and who are eligible for prostatectomy will be invited to participate. Criteria for high-risk prostate cancer include patients with preoperative prostate biopsy score of Gleason 8 (GS8) (Grade group 4 [GG4]) or higher. Patients also need to have a positive PSMA scan on 68-Ga-PSMA-11 PET/CT scan.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The PRELUDE trial is a prospective, non-randomized, single-arm, phase 2 interventional study to assess the oncological outcomes after 2 cycles of Lu-177-PSMA-617 (PluvictoⓇ) administered at 6-week intervals before prostatectomy in patients with high risk localized prostate cancer.

Patients who meet all the inclusion criteria for the study will be enrolled to receive 2 cycles of Lu-177-PSMA-617 (PluvictoⓇ) administered at the dose of 7.4 GBq (±10%), once every 6 weeks (±1 week). Six weeks after the second cycle of Lu-177-PSMA-617 (PluvictoⓇ), patients will be eligible for radical prostatectomy with pelvic lymph node dissection and remain eligible for surgery up until 30 days from this timepoint.

Following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and surgery, all participants will be followed for safety at week 3, 6, 9, 11, and 12 as well as a 30-day safety follow-up visit (FUP) and longer term safety follow-up assessments every 3 months for a period of approximately 2 years. Patients who experience disease progression will be managed according to standard treatment guidelines recommendations.

Study Type

Interventional

Enrollment (Estimated)

54

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Not yet recruiting
        • MedStar Washington Hospital Center
        • Principal Investigator:
          • Ross Krasnow, MD
      • Washington D.C., District of Columbia, United States, 20057
        • Not yet recruiting
        • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
        • Principal Investigator:
          • Paul Leger, MD
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • John Theurer Cancer Center at Hackensack University Medical Center
        • Principal Investigator:
          • Nitin Yerram, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients age 18 or older.
  • Patients with histologically confirmed adenocarcinoma of the prostate.
  • Patients with high-risk disease defined as a preoperative prostate biopsy of Gleason Score 8 (GS8) (Grade group 4 [GG4]) or higher. Men with evidence of lymph node involvement at or below the bifurcation of the common iliac arteries (cN1) on PET-CT 68Ga-PSMA-11 are eligible.
  • Pre-operative, pre-treatment PSMA scan with high expression in prostate confirmed by PET/CT 68Ga-PSMA-11 (greater than liver). Patients must not have any other PET FDG-positive sites outside the prostate.
  • Patients who are able and willing to undergo surgery.

  • Patients with a life expectancy of greater than 10 years. Life expectancy can be estimated using any 1 of the following tools:

    • The Social Security Administration tables:

https://www.ssa.gov/OACT/STATS/table4c6.html

  • The WHO's Life Tables by country:

https://apps.who.int/gho/data/view.main.60000?lang=en

  • The Memorial Sloan Kettering Male Life Expectancy tool:

https://www.mskcc.org/nomograms/prostate

  • If using a life expectancy table, life expectancy should be adjusted using the clinician's assessment of overall health as follows: best quartile of health - add 50%; worst quartile of health - subtract 50%; and middle two quartiles of health - no adjustment. See the NCCN Prostate Cancer Guidelines for more information.

    • Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
    • Patients who agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm, as defined below:
  • With a female partner of childbearing potential who is not pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for 14 weeks after the final dose of study treatment. Men must refrain from donating sperm during this same period.
  • With a pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 14 weeks after the final dose of study treatment to avoid potential exposure to the embryo.

  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not adequate methods of contraception.

    • Patients who are able to comply with follow-up visits and treatment plans.
    • Patients who are able to give informed consent.

Exclusion Criteria:

  • Patients with a prior history of prostate cancer treatment.
  • Patients with previous treatment with PSMA-targeted radioligand therapy or any of the following within 6 months of enrollment confirmation: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation.
  • Patients with distant disease (outside of local lymph nodes).
  • Significant bone marrow impairment defined by leukocytes <3,000/mcL, absolute neutrophil count (ANC) <1,500/mcL, and platelet count lower than 70,000/mcL.
  • Significant liver function impairment defined by total bilirubin higher than 1.5 times the upper limit of normal (ULN), andASL/ALT higher than 3 times the ULN.

  • Impaired kidney function defined by glomerular filtration rate (GFR) lower than 40 mL/min, or concomitant use of nephrotoxic drugs. Kidney function based on eGFR by Modification of Diet in Renal Disease (MDRD) equation:

    • Normal renal function: participants with eGFR 90 mL/min
    • Moderate renal impairment: participants with eGFR 30 to 59 mL/min
    • Severe renal impairment: participants with eGFR 15 to 29 mL/min
  • Patients with significant comorbidities that would make them poor candidates for surgery.
  • Patients with evidence of metastatic disease (enlarged lymph nodes, distant metastatic sites, visceral or bone metastases, etc.).
  • Patients with a history of radiation or hormone therapy to the prostate.
  • Patients with a history of bleeding disorders or who are taking anticoagulant therapy.
  • Patients with active infections or other contraindications for surgery.
  • Patients who are unable or unwilling to give informed consent.
  • Patients who are unable to comply with follow-up visits and treatment plans

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lu-177-PSMA-617 Treatment
Patients will receive 2 cycles of Lu-177-PSMA-617 (PluvictoⓇ) administered at the dose of 7.4 GBq (±10%), once every 6 weeks (±1 week)
Drug: Lu-17-PSMA-617
Lu-17-PSMA-617 administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prostate cancer down-staging following treatment with Lu-177-PSMA-617 (PluvictoⓇ) defined by Gleason Grade Group
Time Frame: Patients will undergo a PSMA PET/CT scans up to week 11 +/- 30 days prior to radical prostatectomy with pelvic lymph node dissection.

Staging of prostate cancer is based on the correlation to Gleason Grade Group (GG) according to the American Joint Committee on Cancer (AJCC; 8TH edition, 2017) staging system for prostate cancer (see Appendix A). Prostate cancer downstaging is defined as the post-treatment stage less than the pre-treatment stage. Different downstaging thresholds will be applied including:

  • Complete downstaging (CD) is defined as no visible tumor in surgical sample;
  • Good response (GR) is defined as downstaging from high risk disease (GG4 or greater) to intermediate risk pathologic disease (GG2 or GG3 disease); and
  • Very good response (VGR) is defined as downstaging from high-risk disease (GG4 or greater) to low risk pathologic disease (GG1 disease).
Patients will undergo a PSMA PET/CT scans up to week 11 +/- 30 days prior to radical prostatectomy with pelvic lymph node dissection.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prostate cancer down-staging following treatment with Lu-177-PSMA-617 (PluvictoⓇ) as defined by margin status, T staging, and seminal vesicle involvement
Time Frame: Patients will undergo a PSMA PET/CT scans up to week 11 +/- 30 days prior to radical prostatectomy with pelvic lymph node dissection.
Staging of prostate cancer is based on the American Joint Committee on Cancer (AJCC; 8TH edition, 2017) combining the TNM staging system for prostate cancer with the Gleason Grade Group (GG)
Patients will undergo a PSMA PET/CT scans up to week 11 +/- 30 days prior to radical prostatectomy with pelvic lymph node dissection.
Decrease in PSMA-avid tumor load
Time Frame: Patients will undergo a SOC PSMA PET/CT scans up to week 11 +/- 30 days prior to radical prostatectomy with pelvic lymph node dissection.
Decrease in PSMA-avid tumor load is measured by comparing the extent of PSMA-avid tumor before and after Lu-177-PSMA-617 (PluvictoⓇ). High PSMA-avidity is defined as more than 2 times the liver activity. Low PSMA-avidity is defined as less than 2 times liver activity. The volumes of PSMA-avid disease will be summed up to quantify the extent of PSMA-avid tumor load before and after Lu-177-PSMA-617 (PluvictoⓇ). PSMA-positive disease is measured using 68Ga-PSMA-11 PET/CT scan.
Patients will undergo a SOC PSMA PET/CT scans up to week 11 +/- 30 days prior to radical prostatectomy with pelvic lymph node dissection.
Safety of radical prostatectomy assessed by surgical delay time
Time Frame: Patients will be assessed for toxicity throughout treatment with Lu-177-PSMA-617 (PluvictoⓇ) and during surgery. Following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and surgery, all participants will be followed for safety with a 30-day safety follow-up
The safety of radical prostatectomy and pelvic lymph node dissection following Lu-177-PSMA-617 (PluvictoⓇ) is defined as the surgical delay time. Surgical delay time is defined as days between the last dose of Lu-177-PSMA-617 (PluvictoⓇ) and the date of radical prostatectomy. All surgeries will be assessed by each surgeon at the end of the procedure and graded as similar to, more difficult than, or significantly more difficult than expected for a high-risk radical prostatectomy (Eapen 2023). Adverse events (AEs) of Lu-177-PSMA-617 (PluvictoⓇ) and surgery will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 or severity grade when CTCAE grading does not exist.
Patients will be assessed for toxicity throughout treatment with Lu-177-PSMA-617 (PluvictoⓇ) and during surgery. Following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and surgery, all participants will be followed for safety with a 30-day safety follow-up
Safety of radical prostatectomy assessed by rate of intraoperative and postoperative complications
Time Frame: Patients will be assessed for toxicity throughout treatment with Lu-177-PSMA-617 (PluvictoⓇ) and during surgery. Following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and surgery, all participants will be followed for safety with a 30-day safety follow-up
The safety of radical prostatectomy and pelvic lymph node dissection following Lu-177-PSMA-617 (PluvictoⓇ) is defined as the rate of intraoperative and postoperative complications. All surgeries will be assessed by each surgeon at the end of the procedure and graded as similar to, more difficult than, or significantly more difficult than expected for a high-risk radical prostatectomy (Eapen 2023). Adverse events (AEs) of Lu-177-PSMA-617 (PluvictoⓇ) and surgery will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 or severity grade when CTCAE grading does not exist.
Patients will be assessed for toxicity throughout treatment with Lu-177-PSMA-617 (PluvictoⓇ) and during surgery. Following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and surgery, all participants will be followed for safety with a 30-day safety follow-up
Safety of radical prostatectomy assessed by the amount of blood loss
Time Frame: Patients will be assessed for toxicity throughout treatment with Lu-177-PSMA-617 (PluvictoⓇ) and during surgery. Following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and surgery, all participants will be followed for safety with a 30-day safety follow-up
The safety of radical prostatectomy and pelvic lymph node dissection following Lu-177-PSMA-617 (PluvictoⓇ) is defined as the amount of blood loss. All surgeries will be assessed by each surgeon at the end of the procedure and graded as similar to, more difficult than, or significantly more difficult than expected for a high-risk radical prostatectomy (Eapen 2023). Adverse events (AEs) of Lu-177-PSMA-617 (PluvictoⓇ) and surgery will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 or severity grade when CTCAE grading does not exist.
Patients will be assessed for toxicity throughout treatment with Lu-177-PSMA-617 (PluvictoⓇ) and during surgery. Following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and surgery, all participants will be followed for safety with a 30-day safety follow-up
Safety of radical prostatectomy assessed by percentage of periprostatic adhesion
Time Frame: Patients will be assessed for toxicity throughout treatment with Lu-177-PSMA-617 (PluvictoⓇ) and during surgery. Following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and surgery, all participants will be followed for safety with a 30-day safety follow-up
The safety of radical prostatectomy and pelvic lymph node dissection following Lu-177-PSMA-617 (PluvictoⓇ) is defined as the percentage of periprostatic adhesion. All surgeries will be assessed by each surgeon at the end of the procedure and graded as similar to, more difficult than, or significantly more difficult than expected for a high-risk radical prostatectomy (Eapen 2023). Adverse events (AEs) of Lu-177-PSMA-617 (PluvictoⓇ) and surgery will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 or severity grade when CTCAE grading does not exist.
Patients will be assessed for toxicity throughout treatment with Lu-177-PSMA-617 (PluvictoⓇ) and during surgery. Following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and surgery, all participants will be followed for safety with a 30-day safety follow-up
Safety of radical prostatectomy assessed by the surgical length of time
Time Frame: Patients will be assessed for toxicity throughout treatment with Lu-177-PSMA-617 (PluvictoⓇ) and during surgery. Following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and surgery, all participants will be followed for safety with a 30-day safety follow-up
The safety of radical prostatectomy and pelvic lymph node dissection following Lu-177-PSMA-617 (PluvictoⓇ) is defined as the surgical length of time. All surgeries will be assessed by each surgeon at the end of the procedure and graded as similar to, more difficult than, or significantly more difficult than expected for a high-risk radical prostatectomy (Eapen 2023). Adverse events (AEs) of Lu-177-PSMA-617 (PluvictoⓇ) and surgery will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 or severity grade when CTCAE grading does not exist.
Patients will be assessed for toxicity throughout treatment with Lu-177-PSMA-617 (PluvictoⓇ) and during surgery. Following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and surgery, all participants will be followed for safety with a 30-day safety follow-up
Quality-of-life and sexual function changes
Time Frame: The EPIC-26 questionnaire will be completed by patients up to 24 months after prostatectomy
Quality-of-life and sexual function changes following treatment with Lu-177-PSMA-617 (PluvictoⓇ) and prostatectomy will be measured using the Expanded Prostate Index Composite (EPIC)-26 questionnaire.
The EPIC-26 questionnaire will be completed by patients up to 24 months after prostatectomy
Biochemical recurrence of prostate cancer at 2 years
Time Frame: PSA levels will be measured up to 24 months after prostatectomy

Biochemical recurrence is defined as a serum prostate-specific antigen (PSA) level more than 0.2 ng/mL on 2 consecutive measurements performed at least 3 months apart.

Timeframe: PSA levels will be measured at screening/baseline, at the initiation of treatment
PSA levels will be measured up to 24 months after prostatectomy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hackensack Meridian Health

Collaborators

Novartis
Lombardi Comprehensive Cancer Center

Investigators

  • Principal Investigator: Nitin Yerram, MD, Hackensack Meridian Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 5, 2025

Primary Completion (Estimated)

March 1, 2029

Study Completion (Estimated)

March 1, 2029

Study Registration Dates

First Submitted

January 17, 2025

First Submitted That Met QC Criteria

January 22, 2025

First Posted (Actual)

January 29, 2025

Study Record Updates

Last Update Posted (Actual)

March 23, 2026

Last Update Submitted That Met QC Criteria

March 20, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro2024-0079 (HMH)
  • PRELUDE (Other Identifier: HMH)
  • CAAA617A1US07T (Other Grant/Funding Number: Novartis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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