Minority-Inclusive Imaging Biomarker-Based End of Therapy Trial for 177Lu-PSMA-617, a Randomized De-Escalation Theranostic Trial for Metastatic Castrate Resistant Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 发起方
- Mayo Clinic
- 入组人数
- 236
- 试验地点
- 2
- 主要终点
- Progression-free survival
研究概览
简要总结
This phase II trial studies how to improve the usage of Lu 177 vipivotide tetraxetan (177Lu-prostate-specific membrane antigen [PSMA]-617) for treating patients with castration-resistant prostate cancer that has spread from where it first started (primary site), to other places in the body (metastatic) utilizing a treatment pause after 5 cycles of therapy versus standard continuous treatment for 6 cycles. Lutetium is a radioligand therapy (RLT). RLT uses a small molecule (in this case 177Lu-PSMA-617) that carries a radioactive component to destroy tumor cells. When lutetium is injected into the body, it attaches to the PSMA receptor found on tumor cells. After lutetium attaches to the PSMA receptor, its radiation component destroys the tumor cell. Giving 177Lu-PSMA-617 for 5 cycles versus 6 cycles may better treat patients with metastatic castrate resistant prostate cancer.
详细描述
PRIMARY OBJECTIVES:
I. To determine whether composite progression-free survival (PFS) per Prostate Cancer Clinical Trials Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, by physician discretion on prostate specific membrane antigen (PSMA)-positron emission tomography (PET), or biochemical progression is non-inferior among patients randomized to treatment pause versus standard treatment in patients with metastatic castrate resistant prostate cancer (mCRPC) who have minimal residual disease on post-therapy single photon emission computed tomography (SPECT) after 2 to 5 cycles of 177Lu-PSMA-617 treatment.
SECONDARY OBJECTIVES:
I. To compare time to subsequent treatment (TTST) in this patient population between randomized arms.
II. To assess time to radiographic progression per PCWG3-modified RECIST 1.1 or by physician discrection on PSMA PET between randomized arms in this patient population between randomized arms.
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
- •REGISTRATION INCLUSION CRITERIA
- •Scheduled at Mayo Clinic Rochester for therapy with 177Lu PSMA-617
- •PSMA positive metastatic castration resistant prostate cancer (68Ga and 18F PSMA PET will be considered equivalent for eligibility) , defined by molecular imaging prostate specific membrane antigen (miPSMA) score >= 2 on Mayo PET report, including interpretation of outside PET or consensus review of PET by nuclear therapy tumor board note in the patient chart
- •Willingness to provide mandatory blood draws for correlative research. (This requirement is waived for patients enrolling after receiving cycle 1 of 177Lu PSMA-617,and achieving a near complete response on post therapy SPECT, as these patients will not be able to provide a pre-treatment baseline blood sample.)
- •Provide written informed consent
- •Ability to complete questionnaire(s) by themselves or with assistance
- •Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
- •RANDOMIZATION INCLUSION CRITERIA
- •Lesions with uptake equal to or above liver on cycle 1 post therapy SPECT, demonstrating that a near complete response on follow up post-therapy scan represents response, rather than sensitivity differences between SPECT and pre-treatment PET
- •Near-complete response on post-therapy SPECT following any of cycles 2-5 of 177Lu PSMA-
- •Near-complete response will be defined as no lesions with SUV max above the mean standard uptake value (SUV) of a representative 2cm spherical region of interest in the central right hepatic lobe, as determined by a nuclear medicine trained radiologist
- •No toxicity that would indicate withholding or reducing dose of the next scheduled cycle of 177Lu PSMA-617 per prescribing information
- •Hemoglobin (Hgb) ≥ 8 g/dL
- •Platelets ≥ 75,000/mm^3
- •Neutrophils ≥ 100/mm^3
- •Estimated glomerular filtration rate (eGFR) < 50 mL/min *body surface area (BSA) using Cockcroft-Gault formula OR
- •Creatinine ≤ 1.5 x upper limit of normal
- •Aspartate transferase (AST) or alanine transaminase (ALT) ≤ 3 x upper limit of normal
- •No other unacceptable toxicity in the clinical judgement of the investigators
- •RE-REGISTRATION INCLUSION CRITERIA (CROSSOVER TO COMPLETION UPON FIRST PROGRESSION OF PATIENTS RANDOMIZED TO TREATMENT PAUSE)
- •First progression in patients randomized to pause treatment
- •PSMA avid lesions on PSMA PET (miPSMA score ≥ 2 following first progression)
排除标准
- •REGISTRATION EXCLUSION CRITERIA
- •Another active malignancy requiring therapy such as radiation, chemotherapy, or immunotherapy
- •Receiving any other investigational agent which would be considered as a treatment for the prostate cancer
- •Failure to recover from acute, reversible effects of prior therapy regardless of interval since last treatment
- •EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at least 3 months since completion of prior treatment
- •Uncontrolled intercurrent non-cardiac illness including, but not limited to:
- •Ongoing or active infection
- •Psychiatric illness/social situations
- •Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
- •Any other conditions that would limit compliance with study requirements
- •Any of the following because this study involves: An investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
- •Persons able to father a child who are unwilling to employ adequate contraception
- •Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- •History of myocardial infarction ≤6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- •RE-REGISTRATION EXCLUSION CRITERIA
- •Serious adverse effect
研究组 & 干预措施
Arm I (177Lu-PSMA-617 standard)
Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients with a near complete response may receive 1 additional cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Biospecimen Collection (Procedure)
Arm I (177Lu-PSMA-617 standard)
Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients with a near complete response may receive 1 additional cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Positron Emission Tomography (Procedure)
Arm I (177Lu-PSMA-617 standard)
Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients with a near complete response may receive 1 additional cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Computed Tomography (Procedure)
Arm II (177Lu-PSMA-617 treatment pause)
Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo clinical observation until documented first progression. After progression, patients resume treatment with 77Lu-PSMA-617 for another cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Questionnaire Administration (Other)
Arm III (Treatment pause 177Lu-PSMA-617)
Patients undergo clinical observation until documented first progression. After progression, patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Clinical Observation (Other)
Arm III (Treatment pause 177Lu-PSMA-617)
Patients undergo clinical observation until documented first progression. After progression, patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Positron Emission Tomography (Procedure)
Arm I (177Lu-PSMA-617 standard)
Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients with a near complete response may receive 1 additional cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Bone Scan (Procedure)
Arm I (177Lu-PSMA-617 standard)
Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients with a near complete response may receive 1 additional cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Lutetium Lu 177 Vipivotide Tetraxetan (Drug)
Arm I (177Lu-PSMA-617 standard)
Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients with a near complete response may receive 1 additional cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Single Photon Emission Computed Tomography (Procedure)
Arm II (177Lu-PSMA-617 treatment pause)
Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo clinical observation until documented first progression. After progression, patients resume treatment with 77Lu-PSMA-617 for another cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Clinical Observation (Other)
Arm II (177Lu-PSMA-617 treatment pause)
Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo clinical observation until documented first progression. After progression, patients resume treatment with 77Lu-PSMA-617 for another cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Computed Tomography (Procedure)
Arm II (177Lu-PSMA-617 treatment pause)
Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo clinical observation until documented first progression. After progression, patients resume treatment with 77Lu-PSMA-617 for another cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Gallium Ga 68 Gozetotide (Other)
Arm II (177Lu-PSMA-617 treatment pause)
Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo clinical observation until documented first progression. After progression, patients resume treatment with 77Lu-PSMA-617 for another cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Lutetium Lu 177 Vipivotide Tetraxetan (Drug)
Arm II (177Lu-PSMA-617 treatment pause)
Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo clinical observation until documented first progression. After progression, patients resume treatment with 77Lu-PSMA-617 for another cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Positron Emission Tomography (Procedure)
Arm II (177Lu-PSMA-617 treatment pause)
Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo clinical observation until documented first progression. After progression, patients resume treatment with 77Lu-PSMA-617 for another cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Single Photon Emission Computed Tomography (Procedure)
Arm III (Treatment pause 177Lu-PSMA-617)
Patients undergo clinical observation until documented first progression. After progression, patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Biospecimen Collection (Procedure)
Arm III (Treatment pause 177Lu-PSMA-617)
Patients undergo clinical observation until documented first progression. After progression, patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Bone Scan (Procedure)
Arm III (Treatment pause 177Lu-PSMA-617)
Patients undergo clinical observation until documented first progression. After progression, patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Computed Tomography (Procedure)
Arm III (Treatment pause 177Lu-PSMA-617)
Patients undergo clinical observation until documented first progression. After progression, patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Gallium Ga 68 Gozetotide (Other)
Arm III (Treatment pause 177Lu-PSMA-617)
Patients undergo clinical observation until documented first progression. After progression, patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Lutetium Lu 177 Vipivotide Tetraxetan (Drug)
Arm III (Treatment pause 177Lu-PSMA-617)
Patients undergo clinical observation until documented first progression. After progression, patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Questionnaire Administration (Other)
Arm III (Treatment pause 177Lu-PSMA-617)
Patients undergo clinical observation until documented first progression. After progression, patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Single Photon Emission Computed Tomography (Procedure)
Arm II (177Lu-PSMA-617 treatment pause)
Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo clinical observation until documented first progression. After progression, patients resume treatment with 77Lu-PSMA-617 for another cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Bone Scan (Procedure)
Arm II (177Lu-PSMA-617 treatment pause)
Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo clinical observation until documented first progression. After progression, patients resume treatment with 77Lu-PSMA-617 for another cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Biospecimen Collection (Procedure)
Arm I (177Lu-PSMA-617 standard)
Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients with a near complete response may receive 1 additional cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Gallium Ga 68 Gozetotide (Other)
Arm I (177Lu-PSMA-617 standard)
Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients with a near complete response may receive 1 additional cycle. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Progression-free survival
时间窗: Up to 5 years
Progression free survival is defined as the time interval between randomization date and the date of disease progression or death, whichever occurs first. Progression will be defined in keeping with Prostate Cancer Clinical Trials Working Group 3 (PCWG3) guidelines. The median progression free survival of each arm, corresponding 95% confidence intervals, and hazard ratio comparing the treatment arm to the control arm will be reported.
次要结局
- Time to subsequent treatment (TTST)(Up to 5 years)
- Overall survival (OS)(Up to 5 years)
- Time to progression (TTP)(Up to 5 years)
- Incidence of adverse events(Up to 5 years)
- Quality of life - FACT-RNT(Up to 5 years)