Schedule De-Escalation of 177Lu-PSMA-617 for the Treatment of Metastatic Castrate Resistant Prostate Cancer
Minority-Inclusive Imaging Biomarker-Based End of Therapy Trial for 177Lu-PSMA-617, a Randomized De-Escalation Theranostic Trial for Metastatic Castrate Resistant Prostate Cancer
4 other identifiers
interventional
236
1 country
1
Brief Summary
This phase II trial studies how to improve the usage of Lu 177 vipivotide tetraxetan (177Lu-prostate-specific membrane antigen \[PSMA\]-617) for treating patients with castration-resistant prostate cancer that has spread from where it first started (primary site), to other places in the body (metastatic) utilizing a treatment pause after 5 cycles of therapy versus standard continuous treatment for 6 cycles. Lutetium is a radioligand therapy (RLT). RLT uses a small molecule (in this case 177Lu-PSMA-617) that carries a radioactive component to destroy tumor cells. When lutetium is injected into the body, it attaches to the PSMA receptor found on tumor cells. After lutetium attaches to the PSMA receptor, its radiation component destroys the tumor cell. Giving 177Lu-PSMA-617 for 5 cycles versus 6 cycles may better treat patients with metastatic castrate resistant prostate cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2024
Longer than P75 for phase_2
1 active site
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
December 28, 2023
CompletedFirst Posted
Study publicly available on registry
January 10, 2024
CompletedStudy Start
First participant enrolled
May 3, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2029
September 11, 2025
September 1, 2025
5.7 years
December 28, 2023
September 5, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free survival
Progression free survival is defined as the time interval between randomization date and the date of disease progression or death, whichever occurs first. Progression will be defined in keeping with Prostate Cancer Clinical Trials Working Group 3 (PCWG3) guidelines. The median progression free survival of each arm, corresponding 95% confidence intervals, and hazard ratio comparing the treatment arm to the control arm will be reported.
Up to 5 years
Secondary Outcomes (5)
Time to subsequent treatment (TTST)
Up to 5 years
Time to progression (TTP)
Up to 5 years
Overall survival (OS)
Up to 5 years
Incidence of adverse events
Up to 5 years
Quality of life - FACT-RNT
Up to 5 years
Study Arms (3)
Arm I (177Lu-PSMA-617 standard)
ACTIVE COMPARATORPatients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients with a near complete response may receive 1 additional cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
Arm II (177Lu-PSMA-617 treatment pause)
EXPERIMENTALPatients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo clinical observation until documented first progression. After progression, patients resume treatment with 77Lu-PSMA-617 for another cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
Arm III (Treatment pause 177Lu-PSMA-617)
EXPERIMENTALPatients undergo clinical observation until documented first progression. After progression, patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
Interventions
Undergo blood sample collection
Undergo bone scan
Undergo active monitoring
Undergo SPECT/CT or PET/CT
Given IV
Given IV
Undergo PET/CT
Ancillary studies
Undergo SPECT/CT
Eligibility Criteria
You may qualify if:
- Scheduled at Mayo Clinic Rochester for therapy with 177Lu PSMA-617
- PSMA positive metastatic castration resistant prostate cancer (68Ga and 18F PSMA PET will be considered equivalent for eligibility) , defined by molecular imaging prostate specific membrane antigen (miPSMA) score \>= 2 on Mayo PET report, including interpretation of outside PET or consensus review of PET by nuclear therapy tumor board note in the patient chart
- Willingness to provide mandatory blood draws for correlative research. (This requirement is waived for patients enrolling after receiving cycle 1 of 177Lu PSMA-617,and achieving a near complete response on post therapy SPECT, as these patients will not be able to provide a pre-treatment baseline blood sample.)
- Provide written informed consent
- Ability to complete questionnaire(s) by themselves or with assistance
- Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
- Lesions with uptake equal to or above liver on cycle 1 post therapy SPECT, demonstrating that a near complete response on follow up post-therapy scan represents response, rather than sensitivity differences between SPECT and pre-treatment PET
- Near-complete response on post-therapy SPECT following any of cycles 2-5 of 177Lu PSMA-617. Near-complete response will be defined as no lesions with SUV max above the mean standard uptake value (SUV) of a representative 2cm spherical region of interest in the central right hepatic lobe, as determined by a nuclear medicine trained radiologist
- No toxicity that would indicate withholding or reducing dose of the next scheduled cycle of 177Lu PSMA-617 per prescribing information
- Hemoglobin (Hgb) ≥ 8 g/dL
- Platelets ≥ 75,000/mm\^3
- Neutrophils ≥ 100/mm\^3
- Estimated glomerular filtration rate (eGFR) \< 50 mL/min \*body surface area (BSA) using Cockcroft-Gault formula OR
- Creatinine ≤ 1.5 x upper limit of normal
- Aspartate transferase (AST) or alanine transaminase (ALT) ≤ 3 x upper limit of normal
- +3 more criteria
You may not qualify if:
- Another active malignancy requiring therapy such as radiation, chemotherapy, or immunotherapy
- Receiving any other investigational agent which would be considered as a treatment for the prostate cancer
- Failure to recover from acute, reversible effects of prior therapy regardless of interval since last treatment
- EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at least 3 months since completion of prior treatment
- Uncontrolled intercurrent non-cardiac illness including, but not limited to:
- Ongoing or active infection
- Psychiatric illness/social situations
- Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
- Any other conditions that would limit compliance with study requirements
- Any of the following because this study involves: An investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
- Persons able to father a child who are unwilling to employ adequate contraception
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- History of myocardial infarction ≤6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- Serious adverse effect
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mayo Cliniclead
Study Sites (1)
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Matthew P. Thorpe, M.D., Ph.D.
Mayo Clinic in Rochester
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 28, 2023
First Posted
January 10, 2024
Study Start
May 3, 2024
Primary Completion (Estimated)
December 31, 2029
Study Completion (Estimated)
December 31, 2029
Last Updated
September 11, 2025
Record last verified: 2025-09