Phase 2 Randomized Trial of Flexible Dosing Schedule of 177Lu-PSMA-617 for the Treatment of Metastatic Castration-Resistant Prostate Cancer (FLEX-MRT)
A Phase 2 Randomized Trial in Patients With Metastatic Castration Resistant Prostate Cancer to Determine the Efficacy of a Flexible Dosing Schedule of Lu-PSMA Treatment up to 12 Cycles Including Potential Treatment Holiday Periods in Comparison to the Standard Fixed Dosing Schedule of Six Cycles Every Six Weeks (FLEX-MRT)
2 other identifiers
interventional
90
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Aug 2024
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 30, 2023
CompletedFirst Posted
Study publicly available on registry
January 22, 2024
CompletedStudy Start
First participant enrolled
August 1, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2028
March 10, 2026
March 1, 2026
3.4 years
November 30, 2023
March 6, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
2-year survival rate
Will be assessed patients treated with 177Lu-PSMA-617 therapy on a flexible dosing schedule (investigational arm) in comparison to patients treated with the standard fixed dosing schedule of maximum 6 treatments cycles every 6 weeks (control arm). Will be reported using descriptive statistics by means of number and percentage of patients dead 24 months after the first cycle.
From the date of the first cycle of Lu 177 vipivotide tetraxetan (177Lu-prostate-specific membrane antigen [PSMA]-617) therapy, up to 2 years
Secondary Outcomes (9)
Incidence of adverse events
Up to 12 cycles and treatment holiday periods, assessed up to 24 months after first cycle of study treatment
Overall survival
From the date of the first cycle injection of 177Lu-PSMA-617 until death, assessed up to 24 months after first cycle of study treatment
Progression-free survival (PFS)
The date of the first cycle injection of 177Lu-PSMA-617 to the date of first evidence of progression, or death from any cause, whichever occurs first, assessed up to 24 months after first cycle of study treatment
Disease control rate (DCR)
Up to 24 months after first cycle of study treatment
DCR by combined radiographic + PSA response
Up to 24 months after first cycle of study treatment
- +4 more secondary outcomes
Study Arms (2)
Arm I (177Lu-PSMA-617)
EXPERIMENTALPatients 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.
Arm II (177Lu-PSMA-617)
ACTIVE COMPARATORPatients 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.
Interventions
Undergo PSMA PET/CT, SPECT/CT, PET/CT and CT
Given IV
Given IV
Undergo PET/CT
Undergo PSMA PET/CT
Undergo SPECT/CT
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Jonsson Comprehensive Cancer Centerlead
- Novartis Pharmaceuticalscollaborator
Study Sites (1)
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jeremie Calais
UCLA / Jonsson Comprehensive Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 30, 2023
First Posted
January 22, 2024
Study Start
August 1, 2024
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
December 31, 2028
Last Updated
March 10, 2026
Record last verified: 2026-03