Escalating Cycle 1 Dose of Lu-177-PSMA-617 for the Treatment of Metastatic Castration Resistant Prostate Cancer

NCT07682649 | Not Yet Recruiting Phase 1 DMC FDA Drug FDA Device

• 4 other identifiers: UMCC 2023.044NCI-2025-01952HUM00234038R01CA289631
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the safety, side effects, and treatment cycle 1 best dose of Lu-177-PSMA-617 in patients with prostate cancer that keeps growing even when the amount of testosterone in the body is reduced to very low levels (castration-resistant) and has spread from where it first started (primary site) to other places in the body (metastatic). Lu-177-PSMA-617 is a radioactive drug. It binds to a protein called prostate-specific membrane antigen (PSMA), which is found on prostate cancer tumor cells. Lu-177-PSMA-617 gives off radiation that may kill these tumor cells. It is a type of radioconjugate. Lu-177-PSMA-617 is currently used in a series of 6 intravenous infusions of the standard dosage, each separated by 6 weeks from the previous infusion. Investigators have observed that the first therapy administration (cycle 1) delivers better radiation treatment to the cancer than each of the following 5 infusions. Giving an increased dosage of Lu-177-PSMA-617 in treatment cycle 1 may have a better effect on metastatic castration-resistant prostate cancer than the standard dosage. The study does not change the total cumulative activity from what is used in the standard dosage treatment but gives an increased dosage in cycle 1 and reduces the total number of cycles.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT)

  The rate of drug-related adverse events that meet protocol-specified dose-limiting criteria and occur during the time period from administration of cycle 1 dosage up to administration of cycle 2 dosage.

  up to 6 weeks

Secondary Outcomes (4)

• Incidence of treatment related adverse events

  at 6 weeks after first dose and 12 weeks after last dose

• Completion of overall multi-cycle (4-5 cycles) planned treatment course

  Up to 30 weeks

• Biochemical (prostate-specific antigen [PSA]) response

  at 6 weeks after first dose and 12 weeks after last dose

• PSMA PET/CT response

  at 6 weeks after first dose and 12 weeks after last dose

Study Arms (1)

Dose Escalation (Lu-177-PSMA-617)

EXPERIMENTAL

Patients receive Lu-177-PSMA-617 IV on day 1 of each cycle. Dose escalation will occur in cycle 1 only: Level 1: 14.8 GBq (7.4 GBq administered 2 times, 2 days apart) Level 2: 22.2 GBq (7.4 GBq administered 3 times, each 2 days apart) Cycles repeat every 6 weeks for up to 5 cycles for dose level 1 and up to 4 cycles for dose level 2, with the Lu-177-PSMA-617 dose of 7.4 GBq, in the absence of disease progression or unacceptable toxicity. Patients also undergo SPECT/CT scans and receive Ga-68 PSMA-11 and undergo PET/CT after cycle 1.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Gallium Ga 68 Gozetotide; Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Device: Positron Emission Tomography; Other: Questionnaire Administration; Device: Single Photon Emission Computed Tomography; Other: Technetium Tc-99m Sulfur Colloid

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of urine samples

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Dose Escalation (Lu-177-PSMA-617)

Computed Tomography PROCEDURE

Undergo SPECT/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Dose Escalation (Lu-177-PSMA-617)

Gallium Ga 68 Gozetotide OTHER

Given Ga-68 PSMA-11

Also known as: (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

Dose Escalation (Lu-177-PSMA-617)

Lutetium Lu 177 Vipivotide Tetraxetan DRUG

Given IV

Also known as: 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

Dose Escalation (Lu-177-PSMA-617)

Positron Emission Tomography DEVICE

Undergo PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Dose Escalation (Lu-177-PSMA-617)

Questionnaire Administration OTHER

Ancillary studies

Dose Escalation (Lu-177-PSMA-617)

Single Photon Emission Computed Tomography DEVICE

Undergo SPECT/CT

Also known as: 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

Dose Escalation (Lu-177-PSMA-617)

Technetium Tc-99m Sulfur Colloid OTHER

Given IV

Also known as: Tc 99m Sulfur Colloid, Tc-99m SC, Technetium Tc 99m Sulfur Colloid

Dose Escalation (Lu-177-PSMA-617)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be eligible for standard Lu-177-PSMA617 RLT for mCRPC, including PSMA PET/CT scan positive (lesion uptake \> liver uptake by visual assessment)
• Patients must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies (i.e., prior chemotherapy, external beam radiation, brachytherapy, immunotherapy, etc.)
• Patients must be ≥18 years of age
• Patients must have an ECOG performance status of 0 or 1
• Absolute neutrophil count (ANC) ≥ 1500/mm\^3
• Platelet count ≥ 150,000/mm\^3
• Hemoglobin ≥ 10.0 g/dL
• Estimated glomerular filtration rate (EGFR) ≥ 60ml/min
• 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
• Use effective birth control methods during the treatment and for 14 weeks after the last Lu-177-PSMA-617 dose
• Ability to understand and the willingness to sign a written informed consent

You may not qualify if:

• Does not meet criteria for standard Lu-177-PSMA-617 RLT
• Diffuse marrow involvement evident on Ga-68-PSMA PET/CT as assessed by study treating clinician
• Prior RLT
• Unmanageable concurrent bladder outflow obstruction or urinary incontinence
• 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
• Plan to start any additional anti-cancer therapy or investigational agents during study therapy. Anti-cancer therapies include chemotherapy and endocrine therapy

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Specimen Handling; gallium 68 PSMA-11; 68Ga-DKFZ-PSMA-11; Pluvicto; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon; Technetium Tc 99m Sulfur Colloid

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Tomography, Emission-Computed; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Image Enhancement; Photography; Radionuclide Imaging; Tomography; Diagnostic Techniques, Radioisotope; Sulfur Compounds; Inorganic Chemicals; Technetium Compounds

Study Officials

• Kirk A Frey, MD

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer AnswerLine

CONTACT

1-800-865-1125; CancerAnswerLine@med.umich.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2026
• First Posted: July 6, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2031
• Last Updated: July 6, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)