Low PSMA SUV Boost (LPS-Boost): Intensified 177Lu-PSMA-617 Treatment for Patients With Metastatic Castrate-Resistant Prostate Cancer With Low PSMA Expressing Disease

NCT ID: NCT06526299

Last Updated: 2025-11-05

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

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

51 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-29

Study Completion Date

2027-12-31

Brief Summary

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This phase II trial tests how well 177Lu-PSMA-617 works in treating patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and that remains despite treatment (resistant). Lutetium Lu 177 (177Lu), the radioactive (tracer) component being delivered by prostate-specific membrane antigen (PSMA)-617, has physical properties that make it ideal radionuclide (imaging tests that uses a small dose tracer) for treatment of metastatic castrate-resistant prostate cancer (mCRPC). 177Lu-PSMA-617 works by binding to prostate cancer cells and inducing damage to deoxyribonucleic acid (DNA) inside prostate cancer cells. Giving 177Lu-PSMA-617 may improve treatment outcomes for patients with mCRPC.

Detailed Description

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OUTLINE:

Patients receive 177Lu-PSMA-617 intravenously (IV) over 30 minutes on days 1, 8, 50, 57, 99 and 141. Treatment repeats every 7 days for cycles 1 and 3 and every 6 weeks for cycle 2 and subsequent cycles for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA positron emission tomography/computed tomography (PET/CT) during screening and single photon emission computed tomography (SPECT)/CT on study. Patients also undergo CT or magnetic resonance imaging (MRI), bone scan, as well as blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30 days and then every 12 weeks for up to 2 years.

Conditions

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Metastatic Castration-Resistant Prostate Carcinoma Stage IVB Prostate Cancer AJCC v8

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (177Lu-PSMA-617)

Patients receive 177Lu-PSMA-617 IV over 30 minutes on days 1, 8, 50, 57, 99 and 141. Treatment repeats every 7 days for cycles 1 and 3 and every 6 weeks for cycle 2 and subsequent cycles for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA-PET/CT during screening and SPECT/CT on study. Patients also undergo CT or MRI, bone scan, as well as blood sample collection throughout the study.

Group Type EXPERIMENTAL

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 and CT

Lutetium Lu 177 Vipivotide Tetraxetan

Intervention Type DRUG

Given IV

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

PSMA PET-CT Scan

Intervention Type PROCEDURE

Undergo PSMA PET/CT

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Single Photon Emission Computed Tomography

Intervention Type PROCEDURE

Undergo SPECT/CT

Interventions

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Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Bone Scan

Undergo bone scan

Intervention Type PROCEDURE

Computed Tomography

Undergo SPECT/CT and CT

Intervention Type PROCEDURE

Lutetium Lu 177 Vipivotide Tetraxetan

Given IV

Intervention Type DRUG

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

PSMA PET-CT Scan

Undergo PSMA 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

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Biological Sample Collection Biospecimen Collected Specimen Collection Bone Scintigraphy CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan tomography 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 Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI PET-CT (PSMA) Prostate-specific Membrane Antigen PET-CT PSMA PET-CT 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

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Inclusion Criteria

* Patients must have the ability to understand and sign an approved informed consent.
* Patients must have the ability to understand and comply with all protocol requirements.
* Patients must be ≥ 18 years of age.
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
* Patients must have a life expectancy \> 6 months.
* Patients must have histological, pathological, and/or cytological confirmation of prostate cancer.
* Patients must have a positive 68Ga-PSMA PET/CT scan with no PSMA negative lesion, as determined by the Nuclear Medicine site investigator. The presence of PSMA-positive lesions was defined as 68Ga-PSMA-11 uptake greater than that of liver parenchyma in one or more metastatic lesions of any size in any organ system. PSMA negative disease defined as lymph nodes of 2.5 cm or visceral lesions or soft tissue component of a lytic bone lesion of 1.0 cm or larger with uptake less than that of liver parenchyma.
* Patients must have whole body tumor SUVmean of \< 10 on 68Ga-PSMA PET/CT scan, as determined by the Nuclear Medicine site investigator. 68GaPSMA PET/CT will be analyzed using a semi-quantitative approach with MIM software (MIM Software Inc.). The workflow identified whole-body regions of interest (ROIs) with an maximum standardized uptake value (SUVmax) greater than 3 and a lesion size of at least 0.5 mm. The reviewer then manually removes any instances of physiological activity or uptake that are not related to the disease. The method of whole-body quantification will automatically calculate the whole body SUVmean.
* 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) at the most recent evaluation before enrollment.
* Patients must have received at least one androgen receptor pathway inhibitor (ARPI) (such as enzalutamide and/or abiraterone).
* 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 Working Group 3 (PCWG3) criteria, Scher et al 2016).
* Patients must have ≥ 1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging obtained ≤ 45 days prior to beginning study therapy. Measurable disease by per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 is not required, as prostate cancer patients may not have RECIST-measurable disease but have detectable disease on bone scan.
* Patients must have recovered to ≤ grade 2 from all clinically significant toxicities related to prior therapies (i.e. prior chemotherapy, radiation, immunotherapy, etc.).
* White blood cell (WBC) count ≥ 2.5 x 10\^9/L (2.5 x 10\^9/L is equivalent to 2.5 x 10\^3/uL and 2.5 x K/uL and 2.5 x 10\^3/cumm and 2500/uL) OR absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (1.5 x 10\^9/L is equivalent to 1.5 x 10\^3/uL and 1.5 x K/uL and 1.5 x 10\^3/cumm and 1500/uL).
* Platelets ≥ 100 x 10\^9/L (100 x 10\^9/L is equivalent to 100 x 10\^3/uL and 100 x K/uL and 100 x 10\^3/cumm and 100,000/uL).
* Hemoglobin ≥ 9 g/dL (9 g/dL is equivalent to 90 g/L and 5.59 mmol/L).
* Total bilirubin ≤ 1.5 x the institutional upper limit of normal (ULN). For patients with known Gilbert's syndrome ≤ 3 x ULN is permitted.
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 3.0 x ULN OR ≤ 5.0 x ULN for patients with liver metastases.
* Albumin \> 3.0 g/dL (3.0 g/dL is equivalent to 30 g/L).
* Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min.
* HIV-infected patients who are healthy and have a low risk of AIDS-related outcomes are included in this trial. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* For patients who have partners of childbearing potential: Partner and/or patient must use a method of birth control with adequate barrier protection, deemed acceptable by the principal investigator during the study and for 14 weeks after last study drug administration. The patients should not donate sperm throughout the treatment period and for 14 weeks following the last treatment.
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. 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.

Exclusion Criteria

* Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation within 6 months prior to treatment day 1. Previous PSMA-targeted radioligand therapy is not allowed.
* Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy \[including monoclonal antibodies\]) within 30 days prior to treatment day 1.
* Any investigational agents within 30 days prior to treatment day 1.
* Known hypersensitivity to the components of the study therapy or its analogs.
* Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
* Transfusion within 30 days of treatment day 1.
* Patients with a history of central nervous system (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.
* Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
* Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis

INDUSTRY

Sponsor Role collaborator

Society of Nuclear Medicine and Molecular Imaging (SNMMI) Mars Shot Research Fund

UNKNOWN

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Amir Iravani, MD FRACP

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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University of California San Francisco

San Francisco, California, United States

Site Status NOT_YET_RECRUITING

Olive View-University of California Los Angeles Medical Center

Sylmar, California, United States

Site Status NOT_YET_RECRUITING

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Akshata Mathur

Role: CONTACT

206-667-5801

Facility Contacts

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Akshata Mathur

Role: primary

206-667-5801

Other Identifiers

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NCI-2024-05664

Identifier Type: REGISTRY

Identifier Source: secondary_id

20433

Identifier Type: OTHER

Identifier Source: secondary_id

RG1124219

Identifier Type: -

Identifier Source: org_study_id

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