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AzTrials

Metastatic Castration-Resistant Prostate CarcinomaPhase 2NCT06526299

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

A Phase 2 study testing Biospecimen Collection, Bone Scan and Computed Tomography in people with Metastatic Castration-Resistant Prostate Carcinoma and Stage IVB Prostate Cancer AJCC v8, run by University of Washington at 3 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Biospecimen Collection, Bone Scan and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
3 sitesUnited States
Study dates
29 Apr 2025to 31 Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
  • Concurrent bone strengthening agents such as bisphosphonates (such as zolendronic acid) and RANKL inhibitors (such as denosumab) are allowed.
  • 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.
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  • 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.

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Akshata Mathur contact

206-667-5801

nucmedresearch@fredhutch.org

United States3 sites, 3 recruiting

  • University of California San Francisco

    San Francisco, California, 94143

    Thomas Hope

    Recruiting

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

    Akshata Mathur, 206-667-5801, nucmedresearch@fredhutch.org

    Angela Castellanos Rodriguez, MD, MSc

    Recruiting

  • Olive View-University of California Los Angeles Medical Center

    Sylmar, California, 91342

    Jeremie Calais

    Not yet recruiting

Other trials in United States

About this study

Official title: A Phase 2 Study of Biomarker-Modulated PSMA Theranostics

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.

Read the detailed description

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.

Being tested
Biospecimen Collection, Bone Scan, Computed Tomography, Lutetium Lu 177 Vipivotide Tetraxetan, Magnetic Resonance Imaging
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Bone ScanProcedure or surgery

    Also called Bone Scintigraphy

    Undergo bone scan

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo SPECT/CT and CT

  • Lutetium Lu 177 Vipivotide TetraxetanDrug

    Also called 177Lu-labeled PSMA-617, 177Lu-PSMA-617, AAA 617, AAA-617

    Given IV

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • PSMA PET-CT ScanProcedure or surgery

    Also called PET-CT (PSMA), Prostate-specific Membrane Antigen PET-CT, PSMA PET-CT

    Undergo PSMA PET/CT

  • Questionnaire AdministrationOther

    Ancillary studies

  • Single Photon Emission Computed TomographyProcedure or surgery

    Also called Medical Imaging, Single Photon Emission Computed Tomography, Single Photon Emission Tomography, Single-Photon Emission Computed, single-photon emission computed tomography

    Undergo SPECT/CT

Study groups in NCT06526299
Study groupRoleWhat they receive
Treatment (177Lu-PSMA-617)ExperimentalPatients 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.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Procedure: Magnetic Resonance Imaging; Procedure: PSMA PET-CT Scan; Other: Questionnaire Administration; Procedure: Single Photon Emission Computed Tomography

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Prostate-specific antigen (PSA) progression-free survival (PFS)

    PSA progression is defined as a rise in PSA at > 12 weeks by more than 25% and more than 2ng/mL above the nadir (lowest PSA point). Time-to-event endpoints will be analyzed graphically and numerically using the Kaplan-Meier method and summarized in terms of median or 1-year survival point estimates with corresponding 95% confidence intervals.

    Measured: From enrollment to PSA progression or death from any cause, assessed up to 2 years

Secondary outcomes (11)

  1. Incidence of adverse events (AEs)

    AEs will be graded in severity according to the Common Terminology Criteria for Adverse Events version 5.0. Will be analyzed descriptively using summaries of counts and proportions of total and type-specific grade 3/4 AEs across cycles. The maximum toxicity grade per patient of each AE will be derived and presented in table format. The number of patients with grade 3 or higher toxicities (for each toxicity type and overall) will be provided. All AEs will be described, including clinically relevant biochemical and hematological values.

    Measured: Up to 30 days post-treatment

  2. PSA50 response

    Will be determined if an average of 70% of patients who receive the intensified regimen achieve a ≥ 50% PSA reduction in favor of the intensified regimen based on a 1-sample test of binomial proportions with 1-sided alpha = 5%. Local labs will measure PSA levels. Increases and decreases will be tracked to assess PSA responses as per Prostate Cancer Working Group 3 (PCWG3). Will be summarized as proportions with 95% confidence intervals calculated using Wilson's method and visualized using waterfall plots.

    Measured: Up to 30 days post-treatment

  3. Radiographic progression-free survival

    Time to radiographic progression is defined using conventional imaging or death due to any cause, whichever occurs first. Radiographic progression will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 for soft tissue and PCWG3 for bone lesions. Will analyzed based on a 1-sample test of binomial proportions with 1-sided alpha = 5%. Time-to-event endpoints will be analyzed graphically and numerically using the Kaplan-Meier method and summarized in terms of median or 1-year survival point estimates with corresponding 95% confidence intervals.

    Measured: From enrollment to radiographic disease progression or death from any cause, assessed up to 2 years

  4. Overall response rate (ORR)

    ORR is defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR) as measured by RECIST v1.1 response in soft tissue, lymph node and visceral lesions. Will analyzed based on a 1-sample test of binomial proportions with 1-sided alpha = 5%.

    Measured: Up to 2 years

  5. Duration of response (DOR)

    DOR will also be measured in patients with a CR or PR from date of first response to the date of RECIST progression or death. Will analyzed based on a 1-sample test of binomial proportions with 1-sided alpha = 5%.

    Measured: Up to 2 years

  6. Progression-free survival (PFS)

    Clinical progression is defined as the development of signs or symptoms related to prostate cancer as assessed by the physician, initiation of other oncologic treatment or death. Will analyzed based on a 1-sample test of binomial proportions with 1-sided alpha = 5%. Time-to-event endpoints will be analyzed graphically and numerically using the Kaplan-Meier method and summarized in terms of median or 1-year survival point estimates with corresponding 95% confidence intervals.

    Measured: From enrolment to first evidence of radiographic or clinical progression, or PSA PFS, assessed up to 2 years

  7. Overall survival

    Will analyzed based on a 1-sample test of binomial proportions with 1-sided alpha = 5%. Time-to-event endpoints will be analyzed graphically and numerically using the Kaplan-Meier method and summarized in terms of median or 1-year survival point estimates with corresponding 95% confidence intervals.

    Measured: From enrollment to death from any cause, assessed up to 2 years

  8. Pain score

    Pain will be assessed using the Brief Pain Inventory - Short Form to assess the severity of pain and the impact of pain on daily functions. Measured on Scale of 0 to 10, 0 = no pain, 10 = worst pain imaginable. Higher scores reflect more pain severity and more pain interference.

    Measured: Up to 30 days post-treatment

  9. Health-related quality of life: Eastern Cooperative Oncology Group (ECOG) Performance Status scale

    Measures one's level of functioning in terms of ability to care for oneself, daily activity, and physical ability (walking, working, etc.) with a range of 0 to 5. A score of 0 indicates performance without restriction whereas a score of 5 indicates death (a higher score indicates worse functioning).

    Measured: Up to 30 days post-treatment

  10. Health-related quality of life (HRQoL): Functional Assessment of Cancer Therapy Prostate (FACT-P)

    The FACT-P questionnaire will also be administered to assess the HRQoL of prostate cancer patients. The FACT-P is made up of 2 parts: the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire with 27 questions, and the Prostate Cancer Subscale (PCS) with an additional 12 questions. The FACT-G questionnaire measures HRQoL in four different domains: Physical well-being, Functional well-being, Emotional well-being, and Social/Family well-being. The PCS is designed specifically to measure prostate cancer-specific quality of life. Descriptive statistics will be used to summarize the original scores, as well as the change from baseline at each assessment point.

    Each item in both the FACT-G and PCS is rated on a 0 to 4 Likert-type scale, 0 being "not at all" and 4 being "very much", and then combined to produce subscale scores for each domain, as well as global quality of life score, with higher scores representing better quality of life.

    Measured: Up to 30 days post-treatment

  11. Time to pain progression

    Will be assessed by participant responses to the Brief Pain Inventory-Short Form. Pain progression is defined as pain worsening of a 2-point or greater increase on question 3 of the inventory. Will be estimated using Kaplan-Meier method. Mean pain scores and corresponding 95% confidence intervals at each cycle will be visualized. Descriptive statistics will be used to summarize the original scores, as well as the change from baseline at each scheduled assessment time point. Additionally, changes from baseline in the scale and subscale values at the time of each assessment will be summarized. Participants with an evaluable baseline score and at least one evaluable post-baseline score during the treatment period will be included in the change from baseline analyses. The number of participants completing each questionnaire and the number of missing or incomplete assessments will be summarized for each scheduled assessment time point.

    Measured: From enrollment to pain progression, assessed up to 30 days post-treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jul 2024
  2. Study start29 Apr 2025
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
51 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06526299
Sponsor's protocol ID
RG1124219
Other IDs
NCI-2024-05664, 20433
Status last verified
Jul 2026
First submitted
19 Jul 2024
Last updated
7 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biospecimen Collection, Bone Scan and Computed Tomography in people with Metastatic Castration-Resistant Prostate Carcinoma and Stage IVB Prostate Cancer AJCC v8, run by University of Washington at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Akshata Mathur (206-667-5801, nucmedresearch@fredhutch.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Prostate-specific antigen (PSA) progression-free survival (PFS) (time frame: From enrollment to PSA progression or death from any cause, assessed up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06526299.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2026.

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