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

NCT ID: NCT03042468

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2026-08-31

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.

Detailed Description

Phase I dose escalation study with 177Lu-PSMA-617 using dose fractionation regimen will be performed in patients with documented progressive metastatic CRPC. The cumulative 177Lu dose [100 mCi (3.7 GBq) - 600 mCi (22.2 GBq)] will be escalated in up to 6 different dose levels (3 + 3 study design). Additional 10 subjects will be enrolled at the MTD dose level to further assess safety and tolerability and to obtain a preliminary assessment of efficacy. The study will enroll adult males 18 years of age or older with documented progressive metastatic CRPC. The primary objectives are: - To determine the dose limiting toxicity (DLT) of fractionated dose of 177Lu-PSMA-617 - To determine the maximal tolerated and recommended phase II dose of 177Lu-PSMA-617 in a 2-week dose-fractionation regimen Subjects will receive the following study interventions:

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 Subjects will be on this study from screening to end of study (day 85).

The treatment phase comprises of 8 visits over 12 weeks. Patients will be followed until death for survival assessment. Patients removed from study for unacceptable adverse events will be followed until resolution or stabilization of the adverse event. All tests and procedures performed on this study are routine and standard of care except: 68Ga-PSMA-HBED-CC PET/CT scan, administration of investigational agent 177Lu-PSMA-617, research blood samples (CTCs for research, cell-free DNA sample), and PSMA testing on archive tissue.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

All subjects

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

Group Type: EXPERIMENTAL

177Lu-PSMA-617

Intervention Type: DRUG

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

68Ga-PSMA-HBED-CC

Intervention Type: DRUG

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

Interventions

177Lu-PSMA-617

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

Intervention Type: DRUG

68Ga-PSMA-HBED-CC

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologically or cytologically confirmed adenocarcinoma of prostate

2. 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

3. ECOG performance status of 0-2

4. 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.

5. 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)

6. Have previously received taxane chemotherapy, been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy.

7. Age > 18 years

8. 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)
• Platelet count >150,000 x 109/uL (independent of transfusion and/or growth factors within 3 months prior to randomization)
• Serum creatinine <1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault
• Serum total bilirubin <1.5 x ULN (unless due to Gilbert's syndrome in which case direct bilirubin must be normal
• Serum AST and ALT <1.5 x ULN

9. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

1. 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

2. Prior systemic beta-emitting bone-seeking radioisotopes

3. Brain metastases or leptomeningeal disease

4. History of deep vein thrombosis and/or pulmonary embolus within 1 month of study entry

5. 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

6. Radiation therapy for treatment of PCa ≤4 weeks of Day 1 Cycle 1

7. 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.

8. 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

9. 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.

10. Known history of known myelodysplastic syndrome

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Scott Tagawa, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Tulane Cancer Center Clinic

New Orleans, Louisiana, United States

Weill Cornell Medical College

New York, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33465252 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PSMA-617

Identifier Type: OTHER

Identifier Source: secondary_id

1609017542

Identifier Type: -

Identifier Source: org_study_id