Phase 2 Randomized Trial of Flexible Dosing Schedule of 177Lu-PSMA-617 for the Treatment of Metastatic Castration-Resistant Prostate Cancer (FLEX-MRT)

NCT ID: NCT06216249

Last Updated: 2025-02-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-01
• Study Completion Date: 2028-12-31

Brief Summary

In advanced metastatic castration resistant prostate cancer (mCRPC) progressing after chemotherapy and androgen receptor (AR)-targeted therapy 177Lu-PSMA-617 is an effective treatment. 177Lu-PSMA-617 RLT is administered with a fixed schedule: 6 treatment cycles, administered every 6 weeks. However, the optimum number of cycles of 177Lu-PSMA in patients who show good response remains unknown. Some patients may benefit from more than 6 cycles of therapy. Additionally, some patients experience a complete or almost complete response before the last cycle. It is unclear whether these patients benefit from the subsequent remaining treatment cycle(s). A treatment holiday period would spare these patients some exposure to the therapy agent and avoid potentially unnecessary toxicity when treatment efficacy is already maximal and additional treatment effect cannot be expected. This randomized phase 2 study compares a group of patients treated with LuPSMA on a flexible and extended dosing schedule including "treatment holiday" periods (investigational arm, up to 12 cycles, as described below) to a control group treated with a fixed dosing schedule of 6 treatments cycles maximum administered every 6 weeks. The flexible dosing schedule in the investigational arm will be based on single photon emission computed tomography (SPECT)/computed tomography (CT) response assessments obtained 24h after injection of LuPSMA therapy cycle. The response assessment during treatment holiday period will be based on positron emission tomography/computed tomography (PET/CT) every 12 weeks. Single-time point SPECT/CT dosimetry protocol at every cycle will be performed and will allow to determine the number of cycles that subjects may receive under the study without exceeding the kidney dose threshold.

Detailed Description

PRIMARY OBJECTIVE:

I. To assess a potential survival benefit (2-year survival rate) of patients treated with Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) therapy on a flexible dosing schedule including up to 12 cycles and potential "treatment holiday" periods in comparison to patients treated with the standard fixed dosing schedule of maximum 6 treatment cycles every 6 weeks.

SECONDARY OBJECTIVES:

I. To determine the safety of the flexible/extended schedule of 177Lu-PSMA-617 therapy.

II. To compare the overall survival (OS) of the flexible/extended schedule of 177Lu-PSMA-617 therapy to the standard-of-care schedule of 177Lu-PSMA-617 therapy.

III. To compare the progression-free survival (PFS) of the flexible/extended schedule of 177Lu-PSMA-617 therapy to the standard-of-care schedule of 177Lu-PSMA-617 therapy.

IV. To compare the disease control rate (DCR) of the flexible/extended schedule of 177Lu-PSMA-617 therapy to the standard-of-care schedule of 177Lu-PSMA-617 therapy.

V. To compare the impact on bone pain level of the flexible/extended schedule of 177Lu-PSMA-617 therapy to the standard-of-care schedule of 177Lu-PSMA-617 therapy.

VI. To compare the impact on health-related quality of life of the flexible/extended schedule of 177Lu-PSMA-617 therapy to the standard-of-care schedule of 177Lu-PSMA-617 therapy.

EXPLORATORY OBJECTIVE:

I. To determine the dosimetry in organs and tumor lesions of the flexible/extended schedule of 177Lu-PSMA-617 therapy.

OUTLINE: Patients are randomized to one of 2 arms.

ARM I: Patients receive 177Lu-PSMA-617 intravenously (IV) once every 6 weeks on study. Treatment repeats every 6 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo post-therapeutic SPECT/CT at every cycle. The flexible dosing schedule in the investigational arm will be based on prostate specific antigen (PSA) and SPECT/CT response assessments obtained 24h after injection of LuPSMA therapy cycle. Based on their response to therapy, patients may be eligible for "treatment holiday" periods. The monitoring during treatment holiday period will be based on PSMA PET/CT every 12 weeks. If disease progresses patients will re-enter the dosing schedule for up to 12 cycles total, every 6 weeks. Patients also receive gallium Ga-68 gozetotide (68Ga-PSMA-11) IV and undergo prostate-specific membrane antigen positron emission tomography/CT (PSMA PET/CT) on the trial.

ARM II: Patients receive 177Lu-PSMA-617 IV once every 6 weeks on study. Treatment repeats every 6 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo post therapeutic SPECT/CT throughout the trial. Patients also receive 68Ga-PSMA-11 IV and undergo PSMA PET/CT on the trial.

Upon completion of study treatment, patients are followed up every 3 months for 24 months from after first cycle of study treatment.

Conditions

Prostate Carcinoma; Stage IVB Prostate Cancer American Joint Committee on Cancer (AJCC) v8

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I (177Lu-PSMA-617)

Patients receive 177Lu-PSMA-617 IV once every 6 weeks on study. Beginning with the third cycle, treatments may be postponed beyond the 6 weeks interval based on defined response criteria ("treatment holiday" period). Treatment repeats every 6 weeks for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients receive 68Ga-PSMA-11 IV and undergo PSMA PET/CT throughout the trial. Patients also undergo SPECT/CT, PET/CT, or CT on the trial.

Group Type: EXPERIMENTAL

Computed Tomography

Intervention Type: PROCEDURE

Undergo PSMA PET/CT, SPECT/CT, PET/CT and CT

Gallium Ga 68 Gozetotide

Intervention Type: OTHER

Given IV

Lutetium Lu 177 Vipivotide Tetraxetan

Intervention Type: DRUG

Given IV

Positron Emission Tomography

Intervention Type: PROCEDURE

Undergo PET/CT

PSMA PET Scan

Intervention Type: PROCEDURE

Undergo PSMA PET/CT

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Single Photon Emission Computed Tomography

Intervention Type: PROCEDURE

Undergo SPECT/CT

Arm II (177Lu-PSMA-617)

Patients receive 177Lu-PSMA-617 IV once every 6 weeks on study. Treatment repeats every 6 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive 68Ga-PSMA-11 IV and undergo PSMA PET/CT throughout the trial. Patients also undergo SPECT/CT, PET/CT, or CT on the trial.

Group Type: ACTIVE_COMPARATOR

Computed Tomography

Intervention Type: PROCEDURE

Undergo PSMA PET/CT, SPECT/CT, PET/CT and CT

Gallium Ga 68 Gozetotide

Intervention Type: OTHER

Given IV

Lutetium Lu 177 Vipivotide Tetraxetan

Intervention Type: DRUG

Given IV

Positron Emission Tomography

Intervention Type: PROCEDURE

Undergo PET/CT

PSMA PET Scan

Intervention Type: PROCEDURE

Undergo PSMA PET/CT

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Single Photon Emission Computed Tomography

Intervention Type: PROCEDURE

Undergo SPECT/CT

Interventions

Computed Tomography

Undergo PSMA PET/CT, SPECT/CT, PET/CT and CT

Intervention Type: PROCEDURE

Gallium Ga 68 Gozetotide

Given IV

Intervention Type: OTHER

Lutetium Lu 177 Vipivotide Tetraxetan

Given IV

Intervention Type: DRUG

Positron Emission Tomography

Undergo PET/CT

Intervention Type: PROCEDURE

PSMA PET Scan

Undergo PSMA PET/CT

Intervention Type: PROCEDURE

Questionnaire Administration

Ancillary studies

Intervention Type: OTHER

Single Photon Emission Computed Tomography

Undergo SPECT/CT

Intervention Type: PROCEDURE

Other Intervention Names

AAA-517; AAA517; Ga PSMA; [68Ga]GaPSMA-11; AAA 517; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized axial tomography (procedure); Computerized Tomography; CT; CT Scan; tomography; (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; 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; 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; Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron emission tomography (procedure); Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Prostate-specific Membrane Antigen PET; PSMA PET; PSMA-Positron emission tomography; 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

Eligibility Criteria

Inclusion Criteria

• Patients must have prostate cancer proven by histopathology
• Patients must have ≥ 1 metastatic lesion by any imaging (CT, magnetic resonance imaging [MRI], bone scan, PET)
• Patients must have received at least one regimen of chemotherapy for mCRPC
• Patients must have received at least one androgen-receptor signaling inhibitors (ARSI)
• Patients must be eligible by PSMA PET VISION criteria. PSMA PET/CT must be performed within 8 weeks of planned first cycle of 177Lu-PSMA-617
• White blood cell (WBC) ≥ 2,500/ul
• Platelets (PLT) ≥ 100,000/ul
• Hemoglobin (Hb) ≥ 9.0 g/dl
• Absolute neutrophil count (ANC) ≥ 1,500 ul
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Patients must be adults ≥ 18 years of age
• Patients must have the ability to understand and sign an approved informed consent form (ICF)
• Patients must have the ability to understand and comply with all protocol requirements

Exclusion Criteria

• Prior cycle of 177Lu-PSMA-617 therapy
• Less than 6 weeks between last myelosuppressive therapy (including docetaxel, cabazitaxel, strontium-89, samarium-153, rhenium-186, rhenium-188, radium-223, hemi-body irradiation) and first cycle of 177Lu-PSMA-617 therapy
• Glomerular filtration rate (GFR) < 50 ml/min
• Urinary tract obstruction or marked hydronephrosis

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

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Jonsson Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeremie Calais

Role: PRINCIPAL_INVESTIGATOR

UCLA / Jonsson Comprehensive Cancer Center

Locations

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Stephanie Lira

Role: CONTACT

StephanieLira@mednet.ucla.edu

310-206-0596

Facility Contacts

Jeremie Calais

Role: primary

jcalais@mednet.ucla.edu

213-769-9636

Other Identifiers

NCI-2023-07172

Identifier Type: REGISTRY

Identifier Source: secondary_id

23-000931

Identifier Type: -

Identifier Source: org_study_id