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)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- 2-year survival rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Arm I (177Lu-PSMA-617)
Patients 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.
干预措施: Computed Tomography (Procedure)
Arm I (177Lu-PSMA-617)
Patients 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.
干预措施: Gallium Ga 68 Gozetotide (Other)
Arm I (177Lu-PSMA-617)
Patients 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.
干预措施: Lutetium Lu 177 Vipivotide Tetraxetan (Drug)
Arm I (177Lu-PSMA-617)
Patients 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.
干预措施: Positron Emission Tomography (Procedure)
Arm I (177Lu-PSMA-617)
Patients 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.
干预措施: PSMA PET Scan (Procedure)
Arm I (177Lu-PSMA-617)
Patients 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.
干预措施: Questionnaire Administration (Other)
Arm I (177Lu-PSMA-617)
Patients 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.
干预措施: Single Photon Emission Computed Tomography (Procedure)
Arm II (177Lu-PSMA-617)
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.
干预措施: Computed Tomography (Procedure)
Arm II (177Lu-PSMA-617)
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.
干预措施: Gallium Ga 68 Gozetotide (Other)
Arm II (177Lu-PSMA-617)
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.
干预措施: Lutetium Lu 177 Vipivotide Tetraxetan (Drug)
Arm II (177Lu-PSMA-617)
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.
干预措施: Positron Emission Tomography (Procedure)
Arm II (177Lu-PSMA-617)
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.
干预措施: PSMA PET Scan (Procedure)
Arm II (177Lu-PSMA-617)
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.
干预措施: Questionnaire Administration (Other)
Arm II (177Lu-PSMA-617)
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.
干预措施: Single Photon Emission Computed Tomography (Procedure)
结局指标
主要结局
2-year survival rate
时间窗: From the date of the first cycle of Lu 177 vipivotide tetraxetan (177Lu-prostate-specific membrane antigen [PSMA]-617) therapy, up to 2 years
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.
次要结局
- Performance status(Up to 24 months after first cycle of study treatment)
- Incidence of adverse events(Up to 12 cycles and treatment holiday periods, assessed up to 24 months after first cycle of study treatment)
- Health related quality of life (pain)(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)
- Bone pain level(Up to 24 months after first cycle of study treatment)
- Health related quality of life (major symptoms/toxicities)(Up to 24 months after first cycle of study treatment)