Phase I Dose-escalation Study of Fractionated 177Lu-PSMA-617 for Progressive Metastatic CRPC

NCT03042468 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 2 other identifiers: 1609017542PSMA-617
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to find the highest dose level of the study drug, 177Lu-PSMA-617 that can be given without severe side effects for advanced prostate cancer.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (3)

• Number of Subjects With Dose Limiting Toxicity (DLT) of Fractionated Dose of 177Lu-PSMA-617

  Proportion of subjects experiencing a dose limiting toxicity (DLT) of fractionated dose of 177Lu-PSMA-617 by using 3+3 dose escalation was assessed.

  Assessed throughout the DLT period, up to 92 days after starting study drug.

• Number of Subjects That Achieved Cumulative Maximum Tolerated Dose (MTD) Phase II Dose of 177Lu-PSMA-617

  This outcome is measuring the number of subjects that achieved MTD. MTD is defined as the highest dose level with an observed incidence of DLT in no more than one out of six patients treated at a particular dose level. If no DLTs were experienced, then a recommended phase II dose was determined in 2-wk dose-fractionation regimen by using a 3+3 dose escalation design, as no MTD was observed.

  from first dose of study drug to at least 12 weeks of subsequent follow-up evaluations, up to 92 days

• Recommended Phase II Dose of 177Lu-PSMA-617 in a 2-week Dose-fractionation Regimen

  Recommended Phase II dose was determined based on the results of the Phase I portion of the study. Since no Maximum Tolerated Dose was achieved given that no Dose Limiting Toxicities occurred, the Recommended Phase II dose was determined based on the Cohort 5 dose.

  Duration of Phase I, up to 47 months

Secondary Outcomes (6)

• The Rate of PSA Decline Following Fractionated 177Lu-PSMA-617

  from baseline visit to short term follow up visit, approximately 6 months

• Count of Patients That Had a Radiographic Response Rate Measured by RECIST 1.1 With PCWG3 Modifications

  From start of study to progression of disease with at least 12 weeks of subsequent follow-up evaluations, up to 54 months

• Progression-free Survival Measured by PCWG3 (Prostate Cancer Working Group3) Criteria

  Duration of time on study, from baseline to last follow up visit, up to 54 months

• Number of CTC Count Responders

  Duration of study, from screening to EOS visit, up to 12 weeks

• Overall Survival Following Fractionated 177Lu-PSMA-617

  Up to 5 years

Study Arms (1)

All subjects

EXPERIMENTAL

1. 177Lu-PSMA-617 \[50mCi (1.85GBq) - 300mCi (11.1GBq)\] intravenous X2 doses, 2 weeks apart (Visit 1 and 2) 2. 68Ga-PSMA-HBED-CC \[5 ±2mCi or 185 ±74MBq\] intravenous during screening and at 12 weeks with standard imaging

Drug: 177Lu-PSMA-617; Drug: 68Ga-PSMA-HBED-CC

Interventions

177Lu-PSMA-617 DRUG

177Lu-PSMA-617 \[50mCi (1.85GBq) - 300mCi (11.1GBq)\] intravenous X2 doses, 2 weeks apart (Visit 1 and 2)

All subjects

68Ga-PSMA-HBED-CC DRUG

68Ga-PSMA-HBED-CC \[5 ±2mCi or 185 ±74MBq\] intravenous during screening and at 12 weeks with standard imaging

All subjects

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of prostate
• Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria:
• PSA progression
• Objective radiographic progression in soft tissue
• New bone lesions
• ECOG performance status of 0-2
• Have serum testosterone \< 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone orchiectomy.
• Have previously been treated with at least one of the following:
• Androgen receptor signaling inhibitor (such as enzalutamide)
• CYP 17 inhibitor (such as abiraterone acetate)
• Have previously received taxane chemotherapy, been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy.
• Age \> 18 years
• Patients must have normal organ and marrow function as defined below:
• Absolute neutrophil count \>2,000 cells/mm3
• Hemoglobin ≥9 g/dL (independent of transfusion and/or growth factors within 1 month prior to registration)

You may not qualify if:

• Use of investigational drugs or implantation of investigational medical device ≤4 weeks of Cycle 1, Day 1 or current enrollment in investigational drug or device study
• Prior systemic beta-emitting bone-seeking radioisotopes
• Brain metastases or leptomeningeal disease
• History of deep vein thrombosis and/or pulmonary embolus within 1 month of study entry
• Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study
• Radiation therapy for treatment of PCa ≤4 weeks of Day 1 Cycle 1
• Patients on stable dose of bisphosphonates or denosumab, which have been started no less than 4 weeks prior to treatment start, may continue on this medication, however patients are not allowed to initiate bisphosphonate/Denosumab therapy during the DLT-assessment period of the study.
• Having partners of childbearing potential and not willing to use a method of birth control deemed acceptable by the principle investigator and chairperson during the study and for 1 month after last study drug administration
• Currently active other malignancy other than non-melanoma skin cancer. Patients are considered not to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse.
• Known history of known myelodysplastic syndrome

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (2)

Tulane Cancer Center Clinic

New Orleans, Louisiana, 70112, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Related Publications (1)

• Vlachostergios PJ, Niaz MJ, Skafida M, Mosallaie SA, Thomas C, Christos PJ, Osborne JR, Molina AM, Nanus DM, Bander NH, Tagawa ST. Imaging expression of prostate-specific membrane antigen and response to PSMA-targeted beta-emitting radionuclide therapies in metastatic castration-resistant prostate cancer. Prostate. 2021 Apr;81(5):279-285. doi: 10.1002/pros.24104. Epub 2021 Jan 19.

  PMID: 33465252 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Pluvicto; gallium 68 PSMA-11

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Scott Tagawa
• Organization: Weill Cornell Medicine

stt2007@med.cornell.edu

646-962-2027

Study Officials

• Scott Tagawa, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: January 19, 2017
• First Posted: February 3, 2017
• Study Start: December 1, 2016
• Primary Completion: September 30, 2021
• Study Completion (Estimated): August 1, 2026
• Last Updated: September 17, 2025
• Results First Posted: December 13, 2022

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)