Recruiting
Phase 2

177Lu-PSMA-617

Sponsor:

University of Washington

Code:

NCT07698535

Conditions

Metastatic Castration-Resistant Prostate Adenocarcinoma

Stage IVB Prostate Cancer AJCC v8

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Lutetium Lu 177 Vipivotide Tetraxetan

Cell-free Circulating Tumor DNA Assay

Computed Tomography

Docetaxel

PSMA PET Scan

Study Details

Brief summary:

This clinical trial studies whether measuring circulating tumor deoxyribonucleic acid (ctDNA) tumor fraction (TF) can be used to help guide the early stopping (discontinuation) of lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) in patients with castration-resistant prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Many types of tumors tend to lose cells or release different types of cellular products including their deoxyribonucleic acid, which is referred to as ctDNA, into the bloodstream before changes can be seen on scans. Health care providers can measure the level of ctDNA in blood or other bodily fluids to determine which patients are at higher risk for the disease to grow, spread, or get worse or come back after a period of improvement. ctDNA TF is a type of ctDNA measurement. Research has shown ctDNA TF may be a promising way to predict which patients will respond to 177Lu-PSMA-617 treatment. Measuring ctDNA TF may help doctors identify which patients may benefit from changing treatments sooner, which may be an effective way to guide early 177Lu-PSMA-617 treatment discontinuation in patients with metastatic castration-resistant prostate cancer.

Conditions

Metastatic Castration-Resistant Prostate Adenocarcinoma

Stage IVB Prostate Cancer AJCC v8

Study ID

NCT07698535

Start date

Oct 1, 2026

Status verified date

Jul, 2026

Completion date

Jul 5, 2029

Anticipated

Primary completion date

Jul 5, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Willing and able to provide informed consent
  • Adult males ≥ 18 years age
  • History of histologically confirmed adenocarcinoma of the prostate without evidence of neuroendocrine or small cell differentiation. If histology is not available, patients must have metastatic disease typical of prostate cancer (i.e., involving bone or pelvic lymph nodes or para-aortic lymph nodes)
  • Evidence of metastatic disease on bone scan or CT scan
  • Patient must have evidence of castration- resistant prostate cancer as evidenced by PSA progression (per Prostate Cancer Working Group 3 \[PCWG3\] criteria) and a castrate serum testosterone level (i.e., ≤ 50 mg/dL)

  • Serum/plasma 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
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Prior treatment and progression on at least one androgen receptor pathway inhibitor (ARPI), in either castration-sensitive or castration-resistant setting
  • Eligible for treatment with either 177Lu-PSMA-617 or docetaxel as per their respective Food and Drug Administration (FDA) labels
  • Absolute neutrophil count ≥ 1.5 x 10\^9/L
  • Platelet count ≥ 100 x 10\^9/L
  • Hemoglobin ≥ 9 g/dL
  • Creatinine clearance ≥ 50 ml/min (calculated by Cockcroft-Gault formula)
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome (direct bilirubin ≤ 1.5 x ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN, unless liver metastases are present in which case they must be ≤ 5 x ULN. For patients with known Gilbert's Syndrome they must be ≤ 3 x ULN
  • Able to comply with study requirements including provision of peripheral blood samples at specified time points for correlative studies

Exclusion Criteria:

  • Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition that could interfere with patient safety or provision of informed consent to participate in this study
  • Evidence of metastatic neuroendocrine/small cell prostate cancer (NEPC). Note: baseline biopsy is not required
  • Patients receiving any systemic therapy (aside from a luteinizing hormone-releasing hormone \[LHRH\] analogue) or radiotherapy within 2 weeks prior to study treatment
  • Persistent toxicities (CTCAE grade > 2) from prior cancer therapy, excluding alopecia and stable neuropathy
  • Patients considered a poor medical risk due to a serious, uncontrolled medical disorder or active, uncontrolled infection. Examples include, but are not limited to uncontrolled seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent
  • Patients who are known to be serologically positive for human immunodeficiency virus (HIV) and a CD4 count < 200
  • Patients with known active hepatitis (i.e. hepatitis B or C). Prior hepatitis C infection is allowed as long as polymerase chain reaction (PCR) is negative
  • Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
  • Serious cardiac disorder, including but not limited to uncontrolled ventricular arrhythmia, recent (within 12 months) myocardial infarction, resting electrocardiogram (ECG) indicating Fridericia's corrected QT interval prolongation > 500ms, or congenital long QT syndrome
  • Prior systemic chemotherapy with taxane chemotherapy, including in hormone sensitive setting (e.g. docetaxel or cabazitaxel)
  • Brain metastases or active epidural disease (treated epidural disease is permitted)

  • Note: baseline brain imaging is not required
  • Contraindication to prednisone therapy including poorly controlled diabetes mellitus

Study Design

Enrollment

64 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

other: Cycles 1 and 2 (177Lu-PSMA-617, ctDNA testing)

Patients receive 177Lu-PSMA-617 IV over 20-30 minutes 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 also undergo blood sample collection with ctDNA TF testing at baseline and C2D1. Patients with undetectable ctDNA TF (< 3%) on C2D1 continue to receive 177Lu-PSMA-617 as above in the absence of disease progression or unacceptable toxicity. Patients with detectable ctDNA TF (≥ 3%) on C2D1 are randomized to 1 of 2 arms. Additionally, patients undergo PSMA PET during screening, SPECT/CT on study, and additional blood sample collection as well as CT throughout the study.

active comparator: Cycle 3+ Arm I (177Lu-PSMA-617)

Starting with cycle 3, patients receive 177Lu-PSMA-617 IV over 20-30 minutes on day 1 of each cycle. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo PSMA PET during screening, SPECT/CT on study, and additional blood sample collection as well as CT throughout the study.

active comparator: Cycle 3+ Arm II (docetaxel)

Starting with cycle 3, patients receive docetaxel IV on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo PSMA PET during screening, SPECT/CT on study, and additional blood sample collection as well as CT throughout the study.

Interventions

Lutetium Lu 177 Vipivotide Tetraxetan

Given IV

Cell-free Circulating Tumor DNA Assay

Undergo ctDNA TF testing

Computed Tomography

Undergo CT

Docetaxel

Given IV

PSMA PET Scan

Undergo PSMA PET

Single Photon Tomography and Computed Tomography Scan

Undergo SPECT/CT

Biospecimen Collection

Undergo blood sample collection

Primary outcome measure

  • Number and proportion among those recruited with detectable circulating tumor deoxyribonucleic acid (ctDNA) tumor fraction who undergo randomization [ Time Frame: Up to 2 cycles (Cycle length = 6 weeks) ]
  • Number of patients screened, enrolled, evaluable for C2D1 ctDNA tumor fraction and for who cycle 3 is administered [ Time Frame: Up to cycle 3 administration (Cycle length = 6 weeks) ]

Central Contacts and Locations

Central contacts

Michael Schweizer, MD

206-606-6252schweize@uw.edu

Locations

Fred Hutch/University of Washington Cancer Consortium

Recruiting

Seattle, Washington, United States, 98109

Contacts

Michael Schweizer, MD

206-606-6252schweize@uw.edu

Principal Investigator:

Michael Schweizer, MD

More Information

Sponsor

University of Washington

Last update posted

Aug 27, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Washington on 2026-08-27.