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

Clinicaltrials.gov ID: NCT06216249

Status RECRUITING

Phase PHASE2

Age ≥ 18 Years

Enrollments 90

Conditions

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

Drugs

Lutetium Lu 177 Vipivotide Tetraxetan

Summary

The randomized phase 2 FLEX MRT 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) 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 SPECT/CT response assessments obtained 24h after injection of LuPSMA therapy cycle. The response assessment during treatment holiday period will be based on PET/CT every 12 weeks.

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 1 of 2 arms.

ARM I: Patients receive 177Lu-PSMA-617 intravenously (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 gallium Ga 68 gozetotide (68Ga-PSMA-11) IV and undergo prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) throughout the trial. Patients also undergo single photon emission computed tomography (SPECT)/CT, PET/CT, or 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 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.

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

Locations

1 location Found with status Recruiting

Status

RECRUITING

Contact Person

Jeremie Calais
213-769-9636
[email protected]

Principal Investigator

Jeremie Calais

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) ≥ 1500/ul
* Platelets (PLT) ≥ 50.000/ul
* Hemoglobin (Hb) ≥ 8.0 g/dl
* Absolute neutrophil count (ANC) ≥ 1000 mm^3
* 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 of 177Lu-PSMA-617 therapy
* Less than 6 weeks since last myelosuppressive therapy (including docetaxel, cabazitaxel, strontium-89, samarium-153, rhenium-186, rhenium-188, radium-223, hemi-body irradiation)
* Glomerular filtration rate (GFR) < 30 ml/min
* Urinary tract obstruction or marked hydronephrosis

Outcome Measures

Primary Outcome Measures

2-year survival rate

Time Frame: 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 Outcome Measures

Incidence of adverse events

Time Frame: Up to 12 cycles and treatment holiday periods, assessed up to 24 months after first cycle of study treatment

Overall survival

Time Frame: 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)

Time Frame: 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