Summary

Eligibility
for males ages 18 years and up (full criteria)
Location
at Los Angeles, California
Dates
study started
completion around
Principal Investigator
by Jeremie Calais
Headshot of Jeremie Calais
Jeremie Calais

Description

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.

Official Title

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)

Details

PRIMARY OBJECTIVE:

  1. 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:

  1. 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.

  1. 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:

  1. 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.

Keywords

Prostate Carcinoma, Stage IVB Prostate Cancer American Joint Committee on Cancer (AJCC) v8, Prostatic Neoplasms, Edetic Acid, 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid, Gallium 68 PSMA-11, Pluvicto, Computed Tomography, Gallium Ga 68 Gozetotide, Lutetium Lu 177 Vipivotide Tetraxetan, Positron Emission Tomography, PSMA PET Scan, Single Photon Emission Computed Tomography

Eligibility

You can join if…

Open to males ages 18 years and up

  • 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 CAN'T join 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

Location

  • UCLA / Jonsson Comprehensive Cancer Center accepting new patients
    Los Angeles California 90095 United States

Lead Scientist at UCLA

  • Jeremie Calais
    Nuclear medicine physician specialized in cancer imaging and theranostics. Associate Professor, Department of Molecular and Medical Pharmacology at UCLA Director, Theranostics Program, Ahmanson Translational Theranostics Division at UCLA Faculty Member of the Jonsson Comprehensive Cancer Center at UCLA. Faculty Member of the Institute of Urologic Oncology at UCLA.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Jonsson Comprehensive Cancer Center
Links
Sign up for this study
ID
NCT06216249
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 90 study participants
Last Updated