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

Description

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.

Conditions

Prostate Carcinoma, Stage IVB Prostate Cancer American Joint Committee on Cancer (AJCC) V8

Study Overview

Study Details

Study overview

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.

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)

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

Condition
Prostate Carcinoma
Intervention / Treatment

-

Contacts and Locations

Los Angeles

UCLA / Jonsson Comprehensive Cancer Center, Los Angeles, California, United States, 90095

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility 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 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
  • * 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

Ages Eligible for Study

18 Years to

Sexes Eligible for Study

MALE

Accepts Healthy Volunteers

No

Collaborators and Investigators

Jonsson Comprehensive Cancer Center,

Jeremie Calais, PRINCIPAL_INVESTIGATOR, UCLA / Jonsson Comprehensive Cancer Center

Study Record Dates

2028-12-31