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

Официальное название

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)

Обзор

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.

Подробное описание

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.

Вмешательства

• Процедура Computed Tomography
  Undergo PSMA PET/CT, SPECT/CT, PET/CT and CT
• Другое Gallium Ga 68 Gozetotide
  Given IV
• Препарат Lutetium Lu 177 Vipivotide Tetraxetan
  Given IV
• Процедура Positron Emission Tomography
  Undergo PET/CT
• Процедура PSMA PET Scan
  Undergo PSMA PET/CT
• Другое Questionnaire Administration
  Ancillary studies
• Процедура Single Photon Emission Computed Tomography
  Undergo SPECT/CT

Первичные конечные точки

• 2-year survival rate [Срок оценки: From the date of the first cycle of Lu 177 vipivotide tetraxetan (177Lu-prostate-specific membrane antigen [PSMA]-617) therapy, up to 2 years]

Вторичные конечные точки (9)

• Incidence of adverse events [Срок оценки: Up to 12 cycles and treatment holiday periods, assessed up to 24 months after first cycle of study treatment]
• Overall survival [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: Up to 24 months after first cycle of study treatment]
• DCR by combined radiographic + PSA response [Срок оценки: Up to 24 months after first cycle of study treatment]
• Bone pain level [Срок оценки: Up to 24 months after first cycle of study treatment]
• Performance status [Срок оценки: Up to 24 months after first cycle of study treatment]
• Health related quality of life (pain) [Срок оценки: Up to 24 months after first cycle of study treatment]
• Health related quality of life (major symptoms/toxicities) [Срок оценки: Up to 24 months after first cycle of study treatment]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• UCLA / Jonsson Comprehensive Cancer Center — Los Angeles

Публикации

• Holzgreve A, Delker A, Ells Z, Brosch-Lenz J, Unterrainer LM, Nikitas J, Zhu S, Contreras MM, Alam H, Nabong RM, Lira S, Vasilyev A, Chen L, Grogan T, Elashoff D, Meyer CA, Dahlbom M, Czernin J, Calais J. Randomized Phase 2 Trial of an Extended and Flexible Dosing Schedule of 177Lu-PSMA Molecular Radiotherapy in Patients with Metastatic Castration-Resistant Prostate Cancer (FLEX-MRT): Study Protoc PMID 40876952

Идентификаторы

NCT: NCT06216249 · 23-000931 · NCI-2023-07172

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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