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

A Phase 1 Study to Investigate Safety of Escalating Cycle 1 Dose of Lu-177-PSMA-617 Radioligand Therapy (RLT) in Metastatic Castration Resistant Prostate Cancer (mCRPC): The ESCENDO Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Stage IVB Prostate Cancer AJCC v8; Metastatic Castration-Resistant Prostate Carcinoma
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Computed Tomography; Procedure: Biospecimen Collection; Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Other: Gallium Ga 68 Gozetotide; Device: Positron Emission Tomography; Device: Single Photon Emission Computed Tomography; Other: Technetium Tc-99m Sulfur Colloid

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Cancer AnswerLine; Phone Number: 1-800-865-1125; Email: CancerAnswerLine@med.umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Rogel Cancer Center
      • Contact: Cancer AnswerLine; Phone Number: 800-865-1125; Email: CancerAnswerLine@med.umich.edu
      • Principal Investigator: Kirk A. Frey, MD
      • Sub-Investigator: Yuni Dewaraja, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Exclusion criteria for participation in other investigational trials: should not participate during RLT or 30 days prior to start of RLT

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Dose Escalation (Lu-177-PSMA-617); 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.

Other: Questionnaire Administration; Ancillary studies; Procedure: Computed Tomography; Undergo SPECT/CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Procedure: Biospecimen Collection; Undergo collection of urine samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Given IV; Other Names: 177Lu-labeled PSMA-617; 177Lu-PSMA-617; Pluvicto; Lu177-PSMA-617; Lutetium-177-PSMA-617; AAA 617; AAA-617; AAA617; Lutetium Lu 177-PSMA-617; LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN; Other: Gallium Ga 68 Gozetotide; Given Ga-68 PSMA-11; Other Names: (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; 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; AAA 517; AAA-517; AAA517; Device: Positron Emission Tomography; Undergo PET; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Device: Single Photon Emission Computed Tomography; Undergo SPECT/CT; Other Names: ST; Medical Imaging, Single Photon Emission Computed Tomography; Single Photon Emission Tomography; single-photon emission computed tomography; SPECT; SPECT imaging; SPECT SCAN; SPET; tomography, emission computed, single photon; Tomography, Emission-Computed, Single-Photon; Single-Photon Emission Computed; Other: Technetium Tc-99m Sulfur Colloid; Given IV; Other Names: Tc 99m Sulfur Colloid; Tc-99m SC; Technetium Tc 99m Sulfur Colloid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment related adverse events	Any treatment related adverse events of Grade 3 or higher (according to CTCAE v5.0) from time of cycle 1 administration until time of cycle 2 administration and from time of cycle 1 administration until 12 weeks after the last cycle administration	at 6 weeks after first dose and 12 weeks after last dose
Completion of overall multi-cycle (4-5 cycles) planned treatment course	To determine the rate of successful completion of the complete planned treatment course (total of 4 or 5 cycles)	Up to 30 weeks
Biochemical (prostate-specific antigen [PSA]) response	Will be estimated as the proportion of patients with ≥ 50% drop in serum PSA levels from baseline to 6 weeks after first cycle and from baseline to 12 weeks after last cycle	at 6 weeks after first dose and 12 weeks after last dose
PSMA PET/CT response	Will be estimated as the proportion of patients with ≥ 30% drop in PSMA positive tumor volume on PET/CT from baseline to 6 weeks after first cycle and from baseline to 12 weeks after last cycle	at 6 weeks after first dose and 12 weeks after last dose

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Kirk A Frey, MD, University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2031

Study Registration Dates

• First Submitted: June 26, 2026
• First Submitted That Met QC Criteria: June 26, 2026
• First Posted (Actual): July 6, 2026

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Sulfur Compounds; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Inorganic Chemicals; Tomography; Diagnostic Imaging; Image Interpretation, Computer-Assisted; Image Enhancement; Photography; Tomography, Emission-Computed; Radionuclide Imaging; Diagnostic Techniques, Radioisotope; Technetium Compounds; Pluvicto; Technetium Tc 99m Sulfur Colloid; Specimen Handling; gallium 68 PSMA-11; Positron-Emission Tomography; 68Ga-DKFZ-PSMA-11; Tomography, Emission-Computed, Single-Photon
• Other Study ID Numbers: UMCC 2023.044; R01CA289631 (U.S. NIH Grant/Contract); NCI-2025-01952 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); HUM00234038 (Other Identifier: University of Michigan Rogel Cancer Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes