Testing Different Dosing Schedules of the Anti-cancer Drug, Lutetium 177Lu PSMA RLT and Its Effect on Patients With Advanced Prostate Cancer, RECIPROCAL Trial

August 4, 2026 updated by: Alliance for Clinical Trials in Oncology

Radioligand Efficacy Comparison by Initial PSA-Response Outcome in Metastatic CRPC With Lutetium 177Lu PSMA RLT (RECIPROCAL)

This randomized phase III trial examines whether lengthening the dosage interval in an adaptive manner for the prostate cancer drug lutetium 177 Lu PSMA RLT improves quality of life without decreasing lifespan when compared to the standard way this medication is given. This study is for patients with hormone resistant prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body. Hormone resistant prostate cancer often has many cells containing a protein called prostate-specific membrane antigen (PSMA) on their surface. The normal cells in the prostate do not normally express as much PSMA protein on their surface as cancer cells. Lutetium 177 Lu PSMA RLT binds to the PSMA protein on the tumor cells. It builds up in these cells and gives off radiation that may kill them. Typically, this medication is given at the same dose every 6 weeks for up to 6 doses. In this trial, researchers want to see if treatment following the first two doses of lutetium 177 Lu PSMA RLT can be delayed until there is evidence of disease activity. This may be an effective way to improve quality of life without decreasing lifespan in patients with advanced prostate cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The primary and secondary objectives of the study:

PRIMARY OBJECTIVES:

I. To compare the overall survival (OS) of patients with metastatic castration-resistant prostate carcinoma (mCRPC) receiving prostate-specific antigen (PSA) adaptive dosing of lutetium 177 Lu prostate specific membrane antigen radioligand therapy (177Lu PSMA RLT) to that of patients receiving standard dose 177Lu PSMA RLT every 6 weeks.

II. To compare quality of life, as measured by Functional Assessment of Cancer Therapy- Prostate (FACT-P) total scores averaged across the first 30 months, in patients with mCRPC who receive 177Lu PSMA RLT adaptive dosing versus standard dosing.

SECONDARY OBJECTIVES:

I. To compare the duration of treatment between standard dosing and adaptive dosing.

II. To compare the radiographic progression-free survival (rPFS) between the treatment arms.

III. To evaluate and compare the toxicity profile of 177Lu PSMA RLT standard dosing and 177Lu PSMA RLT adaptive dosing.

IV. To compare the nadir PSA and PSA kinetics between standard and adaptive dosing.

V. To compare quality-adjusted life years, which accounts for overall survival and health utility (measured by European Quality of Life Five Dimension Five Level Scale [EQ-5D-5L]), between arms.

VI. To compare pain severity, as measured by the Brief Pain Inventory - Short Form (BPI-SF), between arms at 12 and 30 months.

EXPLORATORY OBJECTIVES:

I. To determine the frequency of tumor genomic aberrations (including but not limited to androgen receptor [AR] mutation/amplification, deoxyribonucleic acid [DNA] repair, retinoblastoma 1 [RB1], phosphatase and tensin homolog [PTEN], TP53) by circulating-tumor deoxyribonucleic acid (ctDNA) in patients achieving > 50% PSA decline versus (vs) < 50% PSA decline after 2 cycles of 177Lu PSMA RLT.

II. To evaluate the relationship between OS and initial PSA response (e.g. ≥ 50% decline in PSA level from baseline [PSA50] vs ≥ 75% decline in PSA level from baseline [PSA75] vs ≥ 90% decline in PSA level from baseline [PSA90]) prior to randomization.

OUTLINE:

PRE-REGISTRATION STEP 0: Patients receive 177Lu PSMA RLT intravenously (IV) on day 1 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve a PSA50 response at cycle (C) 2 day (D) 22 proceed to Step 1.

RANDOMIZATION STEP 1: Patients are randomized to 1 of 2 arms.

ARM 1: Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

ARM 2: Starting cycle 2 day 42, patients undergo blood sample collection and PSA monitoring once every 3 weeks (Q3W) in the absence of disease progression or unacceptable toxicity. Patients with either an absolute PSA rise > 4 ng/dL, PSA rise > 25% above nadir, or clinical progression receive 177Lu PSMA RLT IV three weeks later. Patients then resume PSA monitoring Q3W with adaptive 177Lu PSMA RLT dosing for up to 4 total doses in the absence of disease progression or unacceptable toxicity.

Additionally, all patients undergo blood sample collection, computed tomography (CT), and bone scan throughout the trial and PSMA positron emission tomography (PET) during screening. Patients with a history of brain metastases or with clinical indication also undergo magnetic resonance imaging (MRI) throughout the trial.

After completion of study treatment, patients are followed up every 12 weeks until disease progression and then every 6 months thereafter for 5 years following registration.

Study Type

Interventional

Enrollment (Estimated)

1524

Phase

  • Phase 3

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
    • Alaska
      • Anchorage, Alaska, United States, 99508
    • California
      • Bakersfield, California, United States, 93301
        • Recruiting
        • AIS Cancer Center at San Joaquin Community Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 661-323-4673
        • Principal Investigator:
          • Luis Mariscal
      • Irvine, California, United States, 92618
        • Recruiting
        • City of Hope at Irvine Lennar
        • Contact:
          • Site Public Contact
          • Phone Number: 877-467-3411
        • Principal Investigator:
          • Charles B. Nguyen
      • Irvine, California, United States, 92612
        • Recruiting
        • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
        • Contact:
        • Principal Investigator:
          • Omid Yazdanpanah
      • Orange, California, United States, 92868
        • Recruiting
        • UC Irvine Health/Chao Family Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Omid Yazdanpanah
      • Sacramento, California, United States, 95817
        • Recruiting
        • University of California Davis Comprehensive Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 916-734-3089
        • Principal Investigator:
          • Mamta Parikh
    • Delaware
      • Newark, Delaware, United States, 19713
        • Recruiting
        • Helen F Graham Cancer Center
        • Principal Investigator:
          • Gregory A. Masters
        • Contact:
      • Newark, Delaware, United States, 19713
        • Recruiting
        • Medical Oncology Hematology Consultants PA
        • Principal Investigator:
          • Gregory A. Masters
        • Contact:
    • Georgia
      • Newnan, Georgia, United States, 30265
        • Recruiting
        • CTCA at Southeastern Regional Medical Center
        • Principal Investigator:
          • Bamidele A. Adesunloye
        • Contact:
          • Site Public Contact
          • Phone Number: 770-400-6629
    • Idaho
      • Coeur d'Alene, Idaho, United States, 83814
        • Recruiting
        • Kootenai Health - Coeur d'Alene
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Post Falls, Idaho, United States, 83854
        • Recruiting
        • Kootenai Clinic Cancer Services - Post Falls
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Sandpoint, Idaho, United States, 83864
        • Recruiting
        • Kootenai Clinic Cancer Services - Sandpoint
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University
        • Contact:
        • Principal Investigator:
          • Michael Liu
      • Decatur, Illinois, United States, 62526
        • Recruiting
        • Cancer Care Specialists of Illinois - Decatur
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Decatur, Illinois, United States, 62526
        • Recruiting
        • Decatur Memorial Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Mount Vernon, Illinois, United States, 62864
        • Recruiting
        • SSM Health Good Samaritan
        • Principal Investigator:
          • Jay W. Carlson
        • Contact:
      • O'Fallon, Illinois, United States, 62269
        • Recruiting
        • Cancer Care Center of O'Fallon
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • O'Fallon, Illinois, United States, 62269
        • Recruiting
        • HSHS Saint Elizabeth's Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Warrenville, Illinois, United States, 60555
        • Recruiting
        • Northwestern Medicine Cancer Center Warrenville
        • Contact:
        • Principal Investigator:
          • Michael Liu
      • Zion, Illinois, United States, 60099
        • Recruiting
        • Midwestern Regional Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 844-793-0745
        • Principal Investigator:
          • Walter M. Stadler
    • Iowa
      • Ames, Iowa, United States, 50010
        • Recruiting
        • Mary Greeley Medical Center
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
      • Ames, Iowa, United States, 50010
        • Recruiting
        • McFarland Clinic - Ames
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
      • Ankeny, Iowa, United States, 50023
        • Suspended
        • UI Health Care Mission Cancer and Blood - Ankeny Clinic
      • Boone, Iowa, United States, 50036
        • Suspended
        • McFarland Clinic - Boone
      • Carroll, Iowa, United States, 51401
        • Suspended
        • Saint Anthony Regional Hospital
      • Clive, Iowa, United States, 50325
        • Suspended
        • UI Health Care Mission Cancer and Blood - West Des Moines Clinic
      • Des Moines, Iowa, United States, 50309
        • Recruiting
        • Iowa Methodist Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-6727
        • Principal Investigator:
          • Seema Harichand-Herdt
      • Des Moines, Iowa, United States, 50314
        • Suspended
        • Broadlawns Medical Center
      • Des Moines, Iowa, United States, 50314
        • Suspended
        • UI Health Care Mission Cancer and Blood - Laurel Clinic
      • Des Moines, Iowa, United States, 50309
        • Suspended
        • UI Health Care Mission Cancer and Blood - Des Moines Clinic
      • Fort Dodge, Iowa, United States, 50501
        • Recruiting
        • McFarland Clinic - Trinity Cancer Center
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
      • Fort Dodge, Iowa, United States, 50501
        • Suspended
        • UI Healthcare Mission Cancer and Blood - Fort Dodge
      • Jefferson, Iowa, United States, 50129
        • Suspended
        • McFarland Clinic - Jefferson
      • Marshalltown, Iowa, United States, 50158
        • Recruiting
        • McFarland Clinic - Marshalltown
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
      • Pella, Iowa, United States, 50219
        • Suspended
        • UI Healthcare Mission Cancer and Blood - Pella
      • Waukee, Iowa, United States, 50263
        • Suspended
        • UI Health Care Mission Cancer and Blood - Waukee Clinic
      • West Des Moines, Iowa, United States, 50266
        • Suspended
        • The Iowa Clinic PC
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • Recruiting
        • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
        • Contact:
        • Principal Investigator:
          • Samir Narayan
      • Brownstown, Michigan, United States, 48183
        • Recruiting
        • Henry Ford Cancer Institute-Downriver
        • Principal Investigator:
          • Clara Hwang
        • Contact:
      • Clinton Township, Michigan, United States, 48038
        • Recruiting
        • Henry Ford Macomb Hospital-Clinton Township
        • Principal Investigator:
          • Clara Hwang
        • Contact:
      • Dearborn, Michigan, United States, 48126
        • Recruiting
        • Henry Ford Medical Center-Fairlane
        • Principal Investigator:
          • Clara Hwang
        • Contact:
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Hospital
        • Principal Investigator:
          • Clara Hwang
        • Contact:
      • Jackson, Michigan, United States, 49201
        • Recruiting
        • Allegiance Health
        • Principal Investigator:
          • Clara Hwang
        • Contact:
      • Novi, Michigan, United States, 48377
        • Recruiting
        • Henry Ford Medical Center-Columbus
        • Principal Investigator:
          • Clara Hwang
        • Contact:
      • Pontiac, Michigan, United States, 48341
        • Recruiting
        • Trinity Health Saint Joseph Mercy Oakland Hospital
        • Contact:
        • Principal Investigator:
          • Samir Narayan
      • West Bloomfield, Michigan, United States, 48322
        • Recruiting
        • Henry Ford West Bloomfield Hospital
        • Principal Investigator:
          • Clara Hwang
        • Contact:
      • Wyandotte, Michigan, United States, 48192
        • Recruiting
        • Henry Ford Wyandotte Hospital
        • Principal Investigator:
          • Clara Hwang
        • Contact:
    • Minnesota
      • Burnsville, Minnesota, United States, 55337
        • Suspended
        • Minnesota Oncology - Burnsville
      • Cambridge, Minnesota, United States, 55008
        • Suspended
        • Cambridge Medical Center
      • Coon Rapids, Minnesota, United States, 55433
        • Suspended
        • Mercy Hospital
      • Edina, Minnesota, United States, 55435
        • Suspended
        • Fairview Southdale Hospital
      • Maple Grove, Minnesota, United States, 55369
        • Suspended
        • Fairview Clinics and Surgery Center Maple Grove
      • Maplewood, Minnesota, United States, 55109
        • Suspended
        • Minnesota Oncology Hematology PA-Maplewood
      • Maplewood, Minnesota, United States, 55109
        • Suspended
        • Saint John's Hospital - Healtheast
      • Minneapolis, Minnesota, United States, 55407
        • Suspended
        • Abbott-Northwestern Hospital
      • Minneapolis, Minnesota, United States, 55415
        • Suspended
        • Hennepin County Medical Center
      • New Ulm, Minnesota, United States, 56073
        • Suspended
        • New Ulm Medical Center
      • Princeton, Minnesota, United States, 55371
        • Suspended
        • Fairview Northland Medical Center
      • Robbinsdale, Minnesota, United States, 55422
        • Suspended
        • North Memorial Medical Health Center
      • Saint Cloud, Minnesota, United States, 56303
        • Recruiting
        • Coborn Cancer Center at Saint Cloud Hospital
        • Contact:
        • Principal Investigator:
          • Donald J. Jurgens
      • Saint Louis Park, Minnesota, United States, 55416
        • Suspended
        • Park Nicollet Clinic - Saint Louis Park
      • Saint Paul, Minnesota, United States, 55102
        • Suspended
        • United Hospital
      • Saint Paul, Minnesota, United States, 55101
        • Suspended
        • Regions Hospital
      • Shakopee, Minnesota, United States, 55379
        • Suspended
        • Saint Francis Regional Medical Center
      • Stillwater, Minnesota, United States, 55082
        • Suspended
        • Lakeview Hospital
      • Waconia, Minnesota, United States, 55387
        • Suspended
        • Ridgeview Medical Center
      • Willmar, Minnesota, United States, 56201
        • Suspended
        • Rice Memorial Hospital
      • Woodbury, Minnesota, United States, 55125
        • Suspended
        • Minnesota Oncology Hematology PA-Woodbury
      • Wyoming, Minnesota, United States, 55092
        • Suspended
        • Fairview Lakes Medical Center
    • Missouri
      • Saint Joseph, Missouri, United States, 64506
        • Recruiting
        • Heartland Regional Medical Center
        • Principal Investigator:
          • Jay W. Carlson
        • Contact:
      • St Louis, Missouri, United States, 63131
        • Recruiting
        • Missouri Baptist Medical Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
    • Montana
      • Anaconda, Montana, United States, 59711
        • Recruiting
        • Community Hospital of Anaconda
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Billings, Montana, United States, 59101
        • Recruiting
        • Billings Clinic Cancer Center
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Bozeman, Montana, United States, 59715
        • Recruiting
        • Bozeman Health Deaconess Hospital
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Great Falls, Montana, United States, 59405
        • Suspended
        • Great Falls Clinic
      • Great Falls, Montana, United States, 59405
        • Recruiting
        • Benefis Sletten Cancer Institute
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Havre, Montana, United States, 59501
        • Suspended
        • Hi-Line Sletten Cancer Center
      • Helena, Montana, United States, 59601
        • Suspended
        • Benefis Helena Specialty Center
      • Kalispell, Montana, United States, 59901
        • Recruiting
        • Logan Health Medical Center
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Missoula, Montana, United States, 59804
        • Recruiting
        • Community Medical Center
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Recruiting
        • Memorial Sloan Kettering Basking Ridge
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Deaglan McHugh
      • Cape May Court House, New Jersey, United States, 08210
        • Recruiting
        • AtlantiCare Health Park-Cape May Court House
        • Principal Investigator:
          • James C. Wurzer
        • Contact:
          • Site Public Contact
          • Phone Number: 609-677-7735
      • Egg Harbor, New Jersey, United States, 08234
        • Recruiting
        • AtlantiCare Surgery Center
        • Principal Investigator:
          • James C. Wurzer
        • Contact:
          • Site Public Contact
          • Phone Number: 609-748-7200
      • Middletown, New Jersey, United States, 07748
        • Recruiting
        • Memorial Sloan Kettering Monmouth
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Deaglan McHugh
      • Montvale, New Jersey, United States, 07645
        • Recruiting
        • Memorial Sloan Kettering Bergen
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Deaglan McHugh
      • Pennington, New Jersey, United States, 08534
        • Recruiting
        • Capital Health Medical Center-Hopewell
        • Contact:
        • Principal Investigator:
          • Nikhil Thaker
    • New York
      • Buffalo, New York, United States, 14263
        • Recruiting
        • Roswell Park Cancer Institute
        • Contact:
        • Principal Investigator:
          • Ellis G. Levine
      • Commack, New York, United States, 11725
        • Recruiting
        • Memorial Sloan Kettering Commack
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Deaglan McHugh
      • Harrison, New York, United States, 10604
        • Recruiting
        • Memorial Sloan Kettering Westchester
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Deaglan McHugh
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Deaglan McHugh
      • The Bronx, New York, United States, 10461
        • Recruiting
        • Montefiore Medical Center-Einstein Campus
        • Contact:
        • Principal Investigator:
          • Benjamin A. Gartrell
      • The Bronx, New York, United States, 10467
        • Recruiting
        • Montefiore Medical Center - Moses Campus
        • Contact:
        • Principal Investigator:
          • Benjamin A. Gartrell
      • Uniondale, New York, United States, 11553
        • Recruiting
        • Memorial Sloan Kettering Nassau
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
        • Principal Investigator:
          • Deaglan McHugh
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
      • Fargo, North Dakota, United States, 58122
      • Fargo, North Dakota, United States, 58122
    • Ohio
      • Cleveland, Ohio, United States, 44109
        • Recruiting
        • MetroHealth Medical Center
        • Contact:
        • Principal Investigator:
          • Joseph Attallah
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
        • Principal Investigator:
          • Tyler Gunter
    • Oregon
      • Portland, Oregon, United States, 97213
        • Recruiting
        • Providence Portland Medical Center
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Portland, Oregon, United States, 97225
        • Recruiting
        • Providence Saint Vincent Medical Center
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57104
      • Sioux Falls, South Dakota, United States, 57117-5134
    • Washington
      • Edmonds, Washington, United States, 98026
        • Recruiting
        • Swedish Cancer Institute-Edmonds
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Seattle, Washington, United States, 98122
        • Recruiting
        • Swedish Medical Center-First Hill
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
    • Wisconsin
      • Menomonee Falls, Wisconsin, United States, 53051
        • Recruiting
        • Froedtert Menomonee Falls Hospital
        • Principal Investigator:
          • Kathryn A. Bylow
        • Contact:
          • Site Public Contact
          • Phone Number: 262-257-5100
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin
        • Principal Investigator:
          • Kathryn A. Bylow
        • Contact:
          • Site Public Contact
          • Phone Number: 414-805-3666
      • New Berlin, Wisconsin, United States, 53151
        • Recruiting
        • Froedtert and MCW Moorland Reserve Health Center
        • Principal Investigator:
          • Kathryn A. Bylow
        • Contact:
          • Site Public Contact
          • Phone Number: 414-805-0505
      • New Richmond, Wisconsin, United States, 54017
        • Suspended
        • Cancer Center of Western Wisconsin
      • Oak Creek, Wisconsin, United States, 53154
        • Recruiting
        • Drexel Town Square Health Center
        • Principal Investigator:
          • Kathryn A. Bylow
        • Contact:
          • Site Public Contact
          • Phone Number: 414-805-0505
      • West Bend, Wisconsin, United States, 53095
        • Recruiting
        • Froedtert West Bend Hospital/Kraemer Cancer Center
        • Principal Investigator:
          • Kathryn A. Bylow
        • Contact:
          • Site Public Contact
          • Phone Number: 414-805-0505
    • Wyoming
      • Cheyenne, Wyoming, United States, 82001
        • Suspended
        • Memorial Hospital of Laramie County
      • Cody, Wyoming, United States, 82414
        • Suspended
        • Billings Clinic-Cody

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:

  • PRE-REGISTRATION (STEP 0): Patients must have histological, pathological, and/or cytological confirmation of prostate adenocarcinoma
  • PRE-REGISTRATION (STEP 0): Patients must have a positive PSMA PET/CT scan (either gallium Ga 68 gozetotide [68Ga-PSMA-11], fluorine F 18 piflufolastat [18F- DCFPyl], or fluorine F 18 flotufolastat gallium [18F-rhPSMA-7.3]), as defined as uptake greater than liver with no PSMA negative measurable soft tissue disease
  • PRE-REGISTRATION (STEP 0): PSA greater than 2.0 ng/mL

  • PRE-REGISTRATION (STEP 0): Patients must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria:

    • Serum PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL
    • Soft-tissue progression defined as an increase ≥ 20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions
    • Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan (2+2 Prostate Cancer Clinical Trials Working Group 3 [PCWG3] criteria, Scher et al 2016)
  • PRE-REGISTRATION (STEP 0): Patients must have prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (< 50 ng/dL or < 1.7 nmol/L)

  • PRE-REGISTRATION (STEP 0): Patients must have received at least one androgen receptor pathway inhibitor (ARPI) (to include either apalutamide, darolutamide, enzalutamide, or abiraterone)

    * ARPI must be stopped at least 4 weeks prior to pre-registration

  • PRE-REGISTRATION (STEP 0): Patients must not have previously received a taxane based chemotherapy regimen for mCRPC. Prior docetaxel for metastatic hormone-sensitive prostate carcinoma (mHSPC) or in the neoadjuvant or adjuvant setting is permitted if completed at least 12 months prior to pre-registration
  • PRE-REGISTRATION (STEP 0): Patients must have recovered to ≤ grade 2 from all clinically significant toxicities related to prior therapies (i.e. prior chemotherapy, radiation, immunotherapy, etc.)
  • PRE-REGISTRATION (STEP 0): Patients on a stable bisphosphonate or denosumab regimen for ≥ 30 days prior to pre-registration are eligible
  • PRE-REGISTRATION (STEP 0): Previous treatment with strontium Sr-89 (strontium-89), samarium Sm-153 (samarium-153), rhenium Re 186 (rhenium-186), rhenium Re 188 (rhenium-188), radium Ra 223 (radium-223) or hemi-body irradiation within 6 months prior to pre-registration is not allowed. Previous PSMA-targeted radioligand therapy is not allowed
  • PRE-REGISTRATION (STEP 0): Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies]) within 28 days prior to pre-registration is not allowed
  • PRE-REGISTRATION (STEP 0): Age ≥ 18 years
  • PRE-REGISTRATION (STEP 0): Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
  • PRE-REGISTRATION (STEP 0): Absolute neutrophil count (ANC) ≥ 1,500/mm^3
  • PRE-REGISTRATION (STEP 0): Platelet count ≥ 100,000/mm^3
  • PRE-REGISTRATION (STEP 0): Total bilirubin < 1.5 x upper limit of normal (ULN) or < 3 x ULN in patients with Gilbert's syndrome
  • PRE-REGISTRATION (STEP 0): Creatinine clearance estimated glomerular filtration rate (eGFR) ≥ 40 mL/min/1.73m^2 using the Modification of Diet in Renal Disease (MDRD) equation
  • PRE-REGISTRATION (STEP 0): No acute biliary or urinary obstruction

  • PRE-REGISTRATION (STEP 0): Patients with treated/stable brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression

    * Patients with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast)

  • PRE-REGISTRATION (STEP 0): Patients with known HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
  • PRE-REGISTRATION (STEP 0): For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • PRE-REGISTRATION (STEP 0): Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • PRE-REGISTRATION (STEP 0): Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
  • PRE-REGISTRATION (STEP 0): No investigational agents within 28 days prior to pre-registration
  • PRE-REGISTRATION (STEP 0): No other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy
  • PRE-REGISTRATION (STEP 0): No known hypersensitivity to the components of the study therapy or its analogs
  • PRE-REGISTRATION (STEP 0): No transfusion within 30 days of pre-registration
  • PRE-REGISTRATION (STEP 0): No symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
  • PRE-REGISTRATION (STEP 0): Ability to read and comprehend English or Spanish
  • REGISTRATION (STEP 1): Completion of 2 doses of 177Lu PSMA RLT
  • REGISTRATION (STEP 1): PSA decline ≥ 50% between C1 D1 (screening) and C2 D22 +/-3 days
  • REGISTRATION (STEP 1): ECOG Performance Status ≤ 2
  • REGISTRATION (STEP 1): Absolute neutrophil count (ANC) ≥ 1,500/mm^3
  • REGISTRATION (STEP 1): Platelet count ≥ 100,000/mm^3
  • REGISTRATION (STEP 1): Creatinine clearance eGFR ≥ 40 mL/min/1.73m^2 using the Modification of Diet in Renal Disease (MDRD) equation

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Pre-registration step 0 (177Lu PSMA RLT)
Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve a PSA50 response at C2 D22 proceed to Step 1. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.
Other: Questionnaire Administration
Ancillary studies
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CAT Scan
  • CT Scan
Procedure: Biospecimen Collection
Undergo blood sample collection
Drug: Lutetium Lu 177 Vipivotide Tetraxetan
Given IV
Other Names:
  • Pluvicto
Procedure: MRI
Undergo MRI
Other Names:
  • Magnetic Resonance
  • Magnetic Resonance Imaging
Procedure: Bone Scan
Undergo Bone Scan
Procedure: PSMA PET Scan
Undergo PSMA PET Scan
Active Comparator: Randomization step 1 arm 1 (standard dose 177Lu PSMA RLT)
Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial
Other: Questionnaire Administration
Ancillary studies
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CAT Scan
  • CT Scan
Procedure: Biospecimen Collection
Undergo blood sample collection
Drug: Lutetium Lu 177 Vipivotide Tetraxetan
Given IV
Other Names:
  • Pluvicto
Procedure: MRI
Undergo MRI
Other Names:
  • Magnetic Resonance
  • Magnetic Resonance Imaging
Procedure: Bone Scan
Undergo Bone Scan
Procedure: PSMA PET Scan
Undergo PSMA PET Scan
Experimental: Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )
Starting cycle 2 day 42, patients undergo blood sample collection and PSA monitoring Q3W in the absence of disease progression or unacceptable toxicity. Patients with either an absolute PSA rise > 4 ng/dL, PSA rise > 25% above nadir, or clinical progression receive 177Lu PSMA RLT IV three weeks later. Patients then resume PSA monitoring Q3W with adaptive 177Lu PSMA RLT dosing as above for up to 4 total doses in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.
Other: Questionnaire Administration
Ancillary studies
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CAT Scan
  • CT Scan
Procedure: Biospecimen Collection
Undergo blood sample collection
Drug: Lutetium Lu 177 Vipivotide Tetraxetan
Given IV
Other Names:
  • Pluvicto
Procedure: MRI
Undergo MRI
Other Names:
  • Magnetic Resonance
  • Magnetic Resonance Imaging
Procedure: Bone Scan
Undergo Bone Scan
Procedure: PSMA PET Scan
Undergo PSMA PET Scan
Procedure: Patient Monitoring
Undergo PSA monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: Up to 5 years
Will be calculated as time from randomization until death due to any cause, censoring patients not known to have died at the time of their last follow-up. OS will be compared between the treatment arms using a stratified log rank test
Up to 5 years
Quality of life
Time Frame: Up to 30 months
Will be measured using the Functional Assessment of Cancer Therapy- Prostate (FACT-P) total scores. A repeated measures mixed model will be used to evaluate the between-arm mean difference in FACT-P Total scores across the first 30 months from treatment start. A point estimate of the difference and 95% confidence interval will be reported. Results of formal hypothesis testing will only be reported if adaptive dosing is deemed noninferior to standard dosing with regards to overall survival.
Up to 30 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of treatment
Time Frame: Up to 5 years
Calculated from the first administration of 177Lu PSMA RLT to the last administration of 177Lu PSMA RLT among randomized patients. Summary measures for the duration of treatment will be recorded by arm and the stratified Wilcoxon rank sum statistic will be used to test whether the treatment duration distribution differs between the standard and adaptive dose treatments.
Up to 5 years
Radiographic progression-free survival (rPFS)
Time Frame: Up to 5 years
Will be defined as time from randomization to the to the date of radiographic disease progression per the Prostate Cancer Clinical Trials Working Group 3 criteria or death from any cause, whichever occurs first. Patients who are alive without a disease progression will be censored at the time of their last disease evaluation. rPFS will be compared between the two treatment arms using a stratified logrank test.
Up to 5 years
Rate of Grade 3+ AEs
Time Frame: Up to 5 years
Will be assessed using Common Terminology Criteria for Adverse Events version 5.0. The proportion of patients that experience a grade 3+ AE regardless of attribution will be summarized as the number and percent of patients by treatment arm.
Up to 5 years
Prostate-specific antigen (PSA) response
Time Frame: Prior to randomization
There will be different thresholds used for PSA response, all measured as change from baseline and confirmed at least 3 weeks later by a second PSA test: PSA50 (a ≥ 50% decline), PSA75 (a ≥ 75% decline), and PSA90 (a ≥ 90% decline).
Prior to randomization
Nadir PSA
Time Frame: Up to 5 years
This is the lowest PSA value observed starting from baseline.
Up to 5 years
Pain Severity
Time Frame: Up to 30 months
This will be measured using the Brief Pain Index Short Form (BPI-SF). Estimates and 95% confidence intervals for the mean difference between treatment arms at 12 and 30 months will be generated using a repeated measures mixed model.
Up to 30 months
Quality-adjusted life years
Time Frame: Up to 5 years
This will be calculated from overall survival and health utility as measured by European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L) using an area under the curve approach. Summary statistics for the area under the curve of each arm and a 95% CI for the difference between arms will be reported.
Up to 5 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of tumor genomic aberrations
Time Frame: Up to 3 months
: Investigated tumor genomic aberrations include androgen receptor mutation/amplification, deoxyribonucleic acid repair, retinoblastoma 1, phosphatase and tensin homolog, and TP53. The frequency will be compared between treatment arms using a two-sample t-test (or a Fisher's exact test if more appropriate) among patients with ≥ 50% PSA decline and < 50% PSA decline after 2 cycles of 177Lu PSMA RLT.
Up to 3 months
Association between initial PSA response and OS
Time Frame: Up to 5 years
The median survival time will be computed by the Kaplan-Meier estimator for patients with a pre-randomization PSA response between ≥ 50% and < 75%, ≥ 75% and less than 90%, and ≥ 90%. A log rank test will be used to compare OS between the three groups.
Up to 5 years
Estimate of treatment effect by race
Time Frame: up to 5 years
Estimates of the OS HR and the corresponding 95% CIs by race
up to 5 years
Estimate of treatment effect by ethnicity
Time Frame: up to 5 years
Estimates of the OS HR and the corresponding 95% CIs by ethnicity
up to 5 years

Collaborators and Investigators

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

Sponsor

Alliance for Clinical Trials in Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Thomas Hope, MD, Alliance for Clinical Trials in Oncology

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 31, 2026

Primary Completion (Estimated)

September 9, 2034

Study Completion (Estimated)

September 9, 2034

Study Registration Dates

First Submitted

September 23, 2025

First Submitted That Met QC Criteria

September 23, 2025

First Posted (Actual)

October 1, 2025

Study Record Updates

Last Update Posted (Actual)

August 5, 2026

Last Update Submitted That Met QC Criteria

August 4, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A032304
  • NCI-2025-06146 (Other Identifier: NCI Clinical Trial Reporting Program)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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