Schedule De-Escalation of 177Lu-PSMA-617 for the Treatment of Metastatic Castrate Resistant Prostate Cancer

NCT ID: NCT06200103

Last Updated: 2025-09-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

236 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-05-03

Study Completion Date

2029-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVES:

I. To determine whether composite progression-free survival (PFS) per Prostate Cancer Clinical Trials Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, by physician discretion on prostate specific membrane antigen (PSMA)-positron emission tomography (PET), or biochemical progression is non-inferior among patients randomized to treatment pause versus standard treatment in patients with metastatic castrate resistant prostate cancer (mCRPC) who have minimal residual disease on post-therapy single photon emission computed tomography (SPECT) after 2 to 5 cycles of 177Lu-PSMA-617 treatment.

SECONDARY OBJECTIVES:

I. To compare time to subsequent treatment (TTST) in this patient population between randomized arms.

II. To assess time to radiographic progression per PCWG3-modified RECIST 1.1 or by physician discrection on PSMA PET between randomized arms in this patient population between randomized arms.

III. To assess overall survival (OS) in this patient population between randomized arms.

IV. To compare toxicities in treatment pause versus standard treatment in this patient population.

V. To assess changes in patient quality of life (QOL) as measured by the Functional Assessment of Cancer Therapy - Radionuclide Therapy (FACIT-RNT) for each randomized arm.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I: Patients receive 177Lu-PSMA-617 intravenously (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 68Ga-prostate specific membrane antigen-11 (gallium Ga 68-labeled PSMA-11) IV and undergo positron emission tomography (PET)/computed tomography (CT) during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.

ARM II: Patients 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 during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.

ARM III: Patients 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 during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.

After completion of study treatment, patients are followed up every 12 weeks for up to 2 years or progressive disease.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Castration-Resistant Prostate Carcinoma Stage IVB Prostate Cancer AJCC v8

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Arm I (177Lu-PSMA-617 standard)

Patients 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.

Group Type ACTIVE_COMPARATOR

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Bone Scan

Intervention Type PROCEDURE

Undergo bone scan

Computed Tomography

Intervention Type PROCEDURE

Undergo SPECT/CT or PET/CT

Gallium Ga 68 Gozetotide

Intervention Type OTHER

Given IV

Lutetium Lu 177 Vipivotide Tetraxetan

Intervention Type DRUG

Given IV

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Single Photon Emission Computed Tomography

Intervention Type PROCEDURE

Undergo SPECT/CT

Arm II (177Lu-PSMA-617 treatment pause)

Patients 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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Bone Scan

Intervention Type PROCEDURE

Undergo bone scan

Clinical Observation

Intervention Type OTHER

Undergo active monitoring

Computed Tomography

Intervention Type PROCEDURE

Undergo SPECT/CT or PET/CT

Gallium Ga 68 Gozetotide

Intervention Type OTHER

Given IV

Lutetium Lu 177 Vipivotide Tetraxetan

Intervention Type DRUG

Given IV

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Single Photon Emission Computed Tomography

Intervention Type PROCEDURE

Undergo SPECT/CT

Arm III (Treatment pause 177Lu-PSMA-617)

Patients 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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Bone Scan

Intervention Type PROCEDURE

Undergo bone scan

Clinical Observation

Intervention Type OTHER

Undergo active monitoring

Computed Tomography

Intervention Type PROCEDURE

Undergo SPECT/CT or PET/CT

Gallium Ga 68 Gozetotide

Intervention Type OTHER

Given IV

Lutetium Lu 177 Vipivotide Tetraxetan

Intervention Type DRUG

Given IV

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Single Photon Emission Computed Tomography

Intervention Type PROCEDURE

Undergo SPECT/CT

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Bone Scan

Undergo bone scan

Intervention Type PROCEDURE

Clinical Observation

Undergo active monitoring

Intervention Type OTHER

Computed Tomography

Undergo SPECT/CT or PET/CT

Intervention Type PROCEDURE

Gallium Ga 68 Gozetotide

Given IV

Intervention Type OTHER

Lutetium Lu 177 Vipivotide Tetraxetan

Given IV

Intervention Type DRUG

Positron Emission Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Single Photon Emission Computed Tomography

Undergo SPECT/CT

Intervention Type PROCEDURE

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Biological Sample Collection Biospecimen Collected Specimen Collection Bone Scintigraphy observation CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography CT CT Scan tomography Computerized Tomography (CT) scan (68)Ga labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (68)Ga-labeled Glu-urea-Lys(Ahx)-HBED-CC (68)Ga-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC (68)Gallium-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC (68Ga)Glu-urea-Lys(Ahx)-HBED-CC 68Ga-DKFZ-PSMA-11 68Ga-HBED-CC-PSMA 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC 68Ga-PSMA 68Ga-PSMA-11 68Ga-PSMA-HBED-CC [68Ga] Prostate-specific Membrane Antigen 11 [68Ga]GaPSMA-11 AAA 517 AAA-517 AAA517 Ga PSMA Ga-68 labeled DKFZ-PSMA-11 Ga-68 labeled PSMA-11 GA-68 PSMA-11 Gallium Ga 68 PSMA-11 Gallium Ga 68-labeled PSMA-11 GALLIUM GA-68 GOZETOTIDE Gallium-68 PSMA Gallium-68 PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC GaPSMA PSMA-HBED-CC GA-68 177Lu-labeled PSMA-617 177Lu-PSMA-617 AAA 617 AAA-617 AAA617 Lu177-PSMA-617 Lutetium Lu 177-PSMA-617 LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN Lutetium-177-PSMA-617 Pluvicto Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging PT Medical Imaging, Single Photon Emission Computed Tomography Single Photon Emission Tomography Single-Photon Emission Computed single-photon emission computed tomography SPECT SPECT imaging SPECT SCAN SPET ST tomography, emission computed, single photon Tomography, Emission-Computed, Single-Photon

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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
* No other unacceptable toxicity in the clinical judgement of the investigators
* First progression in patients randomized to pause treatment
* PSMA avid lesions on PSMA PET (miPSMA score ≥ 2 following first progression)

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Matthew P. Thorpe, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic in Rochester

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Clinical Trials Referral Office

Role: primary

855-776-0015

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

NCI-2023-10664

Identifier Type: REGISTRY

Identifier Source: secondary_id

MC231005

Identifier Type: OTHER

Identifier Source: secondary_id

MI-BET

Identifier Type: OTHER

Identifier Source: secondary_id

23-006547

Identifier Type: OTHER

Identifier Source: secondary_id

MC231005

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

177Lu-J591 and 177Lu-PSMA-617 Combination for mCRPC
NCT03545165 TERMINATED PHASE1/PHASE2