Testing Different Dosing Schedules of the Anti-cancer Drug, Lutetium 177Lu PSMA RLT and Its Effect on Patients With Advanced Prostate Cancer, RECIPROCAL Trial
Radioligand Efficacy Comparison by Initial PSA-Response Outcome in Metastatic CRPC With Lutetium 177Lu PSMA RLT (RECIPROCAL)
2 other identifiers
interventional
1,524
1 country
102
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2026
Longer than P75 for phase_3
102 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 23, 2025
CompletedFirst Posted
Study publicly available on registry
October 1, 2025
CompletedStudy Start
First participant enrolled
March 31, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 9, 2034
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 9, 2034
July 2, 2026
July 1, 2026
8.4 years
September 23, 2025
July 1, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Overall survival (OS)
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
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 Outcomes (7)
Duration of treatment
Up to 5 years
Radiographic progression-free survival (rPFS)
Up to 5 years
Rate of Grade 3+ AEs
Up to 5 years
Prostate-specific antigen (PSA) response
Prior to randomization
Nadir PSA
Up to 5 years
- +2 more secondary outcomes
Other Outcomes (4)
Frequency of tumor genomic aberrations
Up to 3 months
Association between initial PSA response and OS
Up to 5 years
Estimate of treatment effect by race
up to 5 years
- +1 more other outcomes
Study Arms (3)
Pre-registration step 0 (177Lu PSMA RLT)
ACTIVE COMPARATORPatients 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.
Randomization step 1 arm 1 (standard dose 177Lu PSMA RLT)
ACTIVE COMPARATORPatients 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
Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )
EXPERIMENTALStarting 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.
Interventions
Given IV
Undergo blood sample collection
Undergo PSA monitoring
Undergo CT
Undergo Bone Scan
Undergo PSMA PET Scan
Undergo MRI
Ancillary studies
Eligibility Criteria
You may qualify if:
- 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
- +25 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (102)
Providence Alaska Medical Center
Anchorage, Alaska, 99508, United States
AIS Cancer Center at San Joaquin Community Hospital
Bakersfield, California, 93301, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612, United States
City of Hope at Irvine Lennar
Irvine, California, 92618, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Helen F Graham Cancer Center
Newark, Delaware, 19713, United States
Medical Oncology Hematology Consultants PA
Newark, Delaware, 19713, United States
CTCA at Southeastern Regional Medical Center
Newnan, Georgia, 30265, United States
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814, United States
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854, United States
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, 83864, United States
Northwestern University
Chicago, Illinois, 60611, United States
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269, United States
HSHS Saint Elizabeth's Hospital
O'Fallon, Illinois, 62269, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555, United States
Midwestern Regional Medical Center
Zion, Illinois, 60099, United States
Mary Greeley Medical Center
Ames, Iowa, 50010, United States
McFarland Clinic - Ames
Ames, Iowa, 50010, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023, United States
McFarland Clinic - Boone
Boone, Iowa, 50036, United States
Saint Anthony Regional Hospital
Carroll, Iowa, 51401, United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325, United States
Iowa Methodist Medical Center
Des Moines, Iowa, 50309, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309, United States
Broadlawns Medical Center
Des Moines, Iowa, 50314, United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314, United States
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, 50501, United States
UI Healthcare Mission Cancer and Blood - Fort Dodge
Fort Dodge, Iowa, 50501, United States
McFarland Clinic - Jefferson
Jefferson, Iowa, 50129, United States
McFarland Clinic - Marshalltown
Marshalltown, Iowa, 50158, United States
UI Healthcare Mission Cancer and Blood - Pella
Pella, Iowa, 50219, United States
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, 50263, United States
The Iowa Clinic PC
West Des Moines, Iowa, 50266, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, 48341, United States
Minnesota Oncology - Burnsville
Burnsville, Minnesota, 55337, United States
Cambridge Medical Center
Cambridge, Minnesota, 55008, United States
Mercy Hospital
Coon Rapids, Minnesota, 55433, United States
Fairview Southdale Hospital
Edina, Minnesota, 55435, United States
Fairview Clinics and Surgery Center Maple Grove
Maple Grove, Minnesota, 55369, United States
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109, United States
Saint John's Hospital - Healtheast
Maplewood, Minnesota, 55109, United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407, United States
Hennepin County Medical Center
Minneapolis, Minnesota, 55415, United States
New Ulm Medical Center
New Ulm, Minnesota, 56073, United States
Fairview Northland Medical Center
Princeton, Minnesota, 55371, United States
North Memorial Medical Health Center
Robbinsdale, Minnesota, 55422, United States
Coborn Cancer Center at Saint Cloud Hospital
Saint Cloud, Minnesota, 56303, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416, United States
Regions Hospital
Saint Paul, Minnesota, 55101, United States
United Hospital
Saint Paul, Minnesota, 55102, United States
Saint Francis Regional Medical Center
Shakopee, Minnesota, 55379, United States
Lakeview Hospital
Stillwater, Minnesota, 55082, United States
Ridgeview Medical Center
Waconia, Minnesota, 55387, United States
Rice Memorial Hospital
Willmar, Minnesota, 56201, United States
Minnesota Oncology Hematology PA-Woodbury
Woodbury, Minnesota, 55125, United States
Fairview Lakes Medical Center
Wyoming, Minnesota, 55092, United States
Heartland Regional Medical Center
Saint Joseph, Missouri, 64506, United States
Missouri Baptist Medical Center
St Louis, Missouri, 63131, United States
Community Hospital of Anaconda
Anaconda, Montana, 59711, United States
Billings Clinic Cancer Center
Billings, Montana, 59101, United States
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715, United States
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405, United States
Great Falls Clinic
Great Falls, Montana, 59405, United States
Hi-Line Sletten Cancer Center
Havre, Montana, 59501, United States
Benefis Helena Specialty Center
Helena, Montana, 59601, United States
Logan Health Medical Center
Kalispell, Montana, 59901, United States
Community Medical Center
Missoula, Montana, 59804, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920, United States
AtlantiCare Health Park-Cape May Court House
Cape May Court House, New Jersey, 08210, United States
AtlantiCare Surgery Center
Egg Harbor, New Jersey, 08234, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Memorial Sloan Kettering Commack
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501, United States
Sanford Broadway Medical Center
Fargo, North Dakota, 58122, United States
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122, United States
MetroHealth Medical Center
Cleveland, Ohio, 44109, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Providence Saint Vincent Medical Center
Portland, Oregon, 97225, United States
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota, 57104, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
Swedish Medical Center-First Hill
Seattle, Washington, 98122, United States
Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin, 53051, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Froedtert and MCW Moorland Reserve Health Center
New Berlin, Wisconsin, 53151, United States
Cancer Center of Western Wisconsin
New Richmond, Wisconsin, 54017, United States
Drexel Town Square Health Center
Oak Creek, Wisconsin, 53154, United States
Froedtert West Bend Hospital/Kraemer Cancer Center
West Bend, Wisconsin, 53095, United States
Memorial Hospital of Laramie County
Cheyenne, Wyoming, 82001, United States
Billings Clinic-Cody
Cody, Wyoming, 82414, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Thomas Hope, MD
Alliance for Clinical Trials in Oncology
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 23, 2025
First Posted
October 1, 2025
Study Start
March 31, 2026
Primary Completion (Estimated)
September 9, 2034
Study Completion (Estimated)
September 9, 2034
Last Updated
July 2, 2026
Record last verified: 2026-07