Radioligand Efficacy Comparison by Initial PSA-Response Outcome in Metastatic CRPC With Lutetium 177Lu PSMA RLT (RECIPROCAL)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,524
- 试验地点
- 136
- 主要终点
- Overall survival (OS)
研究概览
简要总结
This randomized phase III trial examines whether lengthening the dosage interval in an adaptive manner for the prostate cancer drug lutetium 177 Lu PSMA RLT improves quality of life without decreasing lifespan when compared to the standard way this medication is given. This study is for patients with hormone resistant prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body. Hormone resistant prostate cancer often has many cells containing a protein called prostate-specific membrane antigen (PSMA) on their surface. The normal cells in the prostate do not normally express as much PSMA protein on their surface as cancer cells. Lutetium 177 Lu PSMA RLT binds to the PSMA protein on the tumor cells. It builds up in these cells and gives off radiation that may kill them. Typically, this medication is given at the same dose every 6 weeks for up to 6 doses. In this trial, researchers want to see if treatment following the first two doses of lutetium 177 Lu PSMA RLT can be delayed until there is evidence of disease activity. This may be an effective way to improve quality of life without decreasing lifespan in patients with advanced prostate cancer.
详细描述
The primary and secondary objectives of the study:
PRIMARY OBJECTIVES:
I. To compare the overall survival (OS) of patients with metastatic castration-resistant prostate carcinoma (mCRPC) receiving prostate-specific antigen (PSA) adaptive dosing of lutetium 177 Lu prostate specific membrane antigen radioligand therapy (177Lu PSMA RLT) to that of patients receiving standard dose 177Lu PSMA RLT every 6 weeks.
II. To compare quality of life, as measured by Functional Assessment of Cancer Therapy- Prostate (FACT-P) total scores averaged across the first 30 months, in patients with mCRPC who receive 177Lu PSMA RLT adaptive dosing versus standard dosing.
SECONDARY OBJECTIVES:
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
- •PRE-REGISTRATION (STEP 0): Patients must have histological, pathological, and/or cytological confirmation of prostate adenocarcinoma
- •PRE-REGISTRATION (STEP 0): Patients must have a positive PSMA PET/CT scan (either gallium Ga 68 gozetotide [68Ga-PSMA-11], fluorine F 18 piflufolastat [18F- DCFPyl], or fluorine F 18 flotufolastat gallium [18F-rhPSMA-7.3]), as defined as uptake greater than liver with no PSMA negative measurable soft tissue disease
- •PRE-REGISTRATION (STEP 0): PSA greater than 2.0 ng/mL
- •PRE-REGISTRATION (STEP 0): Patients must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria:
- •Serum PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL
- •Soft-tissue progression defined as an increase ≥ 20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions
- •Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan (2+2 Prostate Cancer Clinical Trials Working Group 3 [PCWG3] criteria, Scher et al 2016)
- •PRE-REGISTRATION (STEP 0): Patients must have prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (< 50 ng/dL or < 1.7 nmol/L)
- •PRE-REGISTRATION (STEP 0): Patients must have received at least one androgen receptor pathway inhibitor (ARPI) (to include either apalutamide, darolutamide, enzalutamide, or abiraterone)
- •* ARPI must be stopped at least 4 weeks prior to pre-registration
- •PRE-REGISTRATION (STEP 0): Patients must not have previously received a taxane based chemotherapy regimen for mCRPC. Prior docetaxel for metastatic hormone-sensitive prostate carcinoma (mHSPC) or in the neoadjuvant or adjuvant setting is permitted if completed at least 12 months prior to pre-registration
- •PRE-REGISTRATION (STEP 0): Patients must have recovered to ≤ grade 2 from all clinically significant toxicities related to prior therapies (i.e. prior chemotherapy, radiation, immunotherapy, etc.)
- •PRE-REGISTRATION (STEP 0): Patients on a stable bisphosphonate or denosumab regimen for ≥ 30 days prior to pre-registration are eligible
- •PRE-REGISTRATION (STEP 0): Previous treatment with strontium Sr-89 (strontium-89), samarium Sm-153 (samarium-153), rhenium Re 186 (rhenium-186), rhenium Re 188 (rhenium-188), radium Ra 223 (radium-223) or hemi-body irradiation within 6 months prior to pre-registration is not allowed. Previous PSMA-targeted radioligand therapy is not allowed
- •PRE-REGISTRATION (STEP 0): Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies]) within 28 days prior to pre-registration is not allowed
- •PRE-REGISTRATION (STEP 0): Age ≥ 18 years
- •PRE-REGISTRATION (STEP 0): Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
- •PRE-REGISTRATION (STEP 0): Absolute neutrophil count (ANC) ≥ 1,500/mm^3
- •PRE-REGISTRATION (STEP 0): Platelet count ≥ 100,000/mm^3
- •PRE-REGISTRATION (STEP 0): Total bilirubin < 1.5 x upper limit of normal (ULN) or < 3 x ULN in patients with Gilbert's syndrome
- •PRE-REGISTRATION (STEP 0): Creatinine clearance estimated glomerular filtration rate (eGFR) ≥ 40 mL/min/1.73m^2 using the Modification of Diet in Renal Disease (MDRD) equation
- •PRE-REGISTRATION (STEP 0): No acute biliary or urinary obstruction
- •PRE-REGISTRATION (STEP 0): Patients with treated/stable brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
- •* Patients with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast)
- •PRE-REGISTRATION (STEP 0): Patients with known HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
- •PRE-REGISTRATION (STEP 0): For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- •PRE-REGISTRATION (STEP 0): Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- •PRE-REGISTRATION (STEP 0): Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
- •PRE-REGISTRATION (STEP 0): No investigational agents within 28 days prior to pre-registration
- •PRE-REGISTRATION (STEP 0): No other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy
- •PRE-REGISTRATION (STEP 0): No known hypersensitivity to the components of the study therapy or its analogs
- •PRE-REGISTRATION (STEP 0): No transfusion within 30 days of pre-registration
- •PRE-REGISTRATION (STEP 0): No symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
- •PRE-REGISTRATION (STEP 0): Ability to read and comprehend English or Spanish
- •REGISTRATION (STEP 1): Completion of 2 doses of 177Lu PSMA RLT
- •REGISTRATION (STEP 1): PSA decline ≥ 50% between C1 D1 (screening) and C2 D22 +/-3 days
- •REGISTRATION (STEP 1): ECOG Performance Status ≤ 2
- •REGISTRATION (STEP 1): Absolute neutrophil count (ANC) ≥ 1,500/mm^3
- •REGISTRATION (STEP 1): Platelet count ≥ 100,000/mm^3
- •REGISTRATION (STEP 1): Creatinine clearance eGFR ≥ 40 mL/min/1.73m^2 using the Modification of Diet in Renal Disease (MDRD) equation
排除标准
- 未提供
研究组 & 干预措施
Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )
Starting cycle 2 day 42, patients undergo blood sample collection and PSA monitoring Q3W in the absence of disease progression or unacceptable toxicity. Patients with either an absolute PSA rise > 4 ng/dL, PSA rise > 25% above nadir, or clinical progression receive 177Lu PSMA RLT IV three weeks later. Patients then resume PSA monitoring Q3W with adaptive 177Lu PSMA RLT dosing as above for up to 4 total doses in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.
干预措施: Questionnaire Administration (Other)
Randomization step 1 arm 1 (standard dose 177Lu PSMA RLT)
Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial
干预措施: Biospecimen Collection (Procedure)
Randomization step 1 arm 1 (standard dose 177Lu PSMA RLT)
Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial
干预措施: PSMA PET Scan (Procedure)
Randomization step 1 arm 1 (standard dose 177Lu PSMA RLT)
Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial
干预措施: Questionnaire Administration (Other)
Randomization step 1 arm 1 (standard dose 177Lu PSMA RLT)
Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial
干预措施: Computed Tomography (Procedure)
Randomization step 1 arm 1 (standard dose 177Lu PSMA RLT)
Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial
干预措施: Bone Scan (Procedure)
Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )
Starting cycle 2 day 42, patients undergo blood sample collection and PSA monitoring Q3W in the absence of disease progression or unacceptable toxicity. Patients with either an absolute PSA rise > 4 ng/dL, PSA rise > 25% above nadir, or clinical progression receive 177Lu PSMA RLT IV three weeks later. Patients then resume PSA monitoring Q3W with adaptive 177Lu PSMA RLT dosing as above for up to 4 total doses in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.
干预措施: Lutetium Lu 177 Vipivotide Tetraxetan (Drug)
Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )
Starting cycle 2 day 42, patients undergo blood sample collection and PSA monitoring Q3W in the absence of disease progression or unacceptable toxicity. Patients with either an absolute PSA rise > 4 ng/dL, PSA rise > 25% above nadir, or clinical progression receive 177Lu PSMA RLT IV three weeks later. Patients then resume PSA monitoring Q3W with adaptive 177Lu PSMA RLT dosing as above for up to 4 total doses in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.
干预措施: Biospecimen Collection (Procedure)
Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )
Starting cycle 2 day 42, patients undergo blood sample collection and PSA monitoring Q3W in the absence of disease progression or unacceptable toxicity. Patients with either an absolute PSA rise > 4 ng/dL, PSA rise > 25% above nadir, or clinical progression receive 177Lu PSMA RLT IV three weeks later. Patients then resume PSA monitoring Q3W with adaptive 177Lu PSMA RLT dosing as above for up to 4 total doses in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.
干预措施: Patient Monitoring (Procedure)
Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )
Starting cycle 2 day 42, patients undergo blood sample collection and PSA monitoring Q3W in the absence of disease progression or unacceptable toxicity. Patients with either an absolute PSA rise > 4 ng/dL, PSA rise > 25% above nadir, or clinical progression receive 177Lu PSMA RLT IV three weeks later. Patients then resume PSA monitoring Q3W with adaptive 177Lu PSMA RLT dosing as above for up to 4 total doses in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.
干预措施: Computed Tomography (Procedure)
Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )
Starting cycle 2 day 42, patients undergo blood sample collection and PSA monitoring Q3W in the absence of disease progression or unacceptable toxicity. Patients with either an absolute PSA rise > 4 ng/dL, PSA rise > 25% above nadir, or clinical progression receive 177Lu PSMA RLT IV three weeks later. Patients then resume PSA monitoring Q3W with adaptive 177Lu PSMA RLT dosing as above for up to 4 total doses in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.
干预措施: PSMA PET Scan (Procedure)
Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )
Starting cycle 2 day 42, patients undergo blood sample collection and PSA monitoring Q3W in the absence of disease progression or unacceptable toxicity. Patients with either an absolute PSA rise > 4 ng/dL, PSA rise > 25% above nadir, or clinical progression receive 177Lu PSMA RLT IV three weeks later. Patients then resume PSA monitoring Q3W with adaptive 177Lu PSMA RLT dosing as above for up to 4 total doses in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.
干预措施: MRI (Procedure)
Pre-registration step 0 (177Lu PSMA RLT)
Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve a PSA50 response at C2 D22 proceed to Step 1. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.
干预措施: Biospecimen Collection (Procedure)
Pre-registration step 0 (177Lu PSMA RLT)
Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve a PSA50 response at C2 D22 proceed to Step 1. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.
干预措施: Lutetium Lu 177 Vipivotide Tetraxetan (Drug)
Randomization step 1 arm 1 (standard dose 177Lu PSMA RLT)
Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial
干预措施: MRI (Procedure)
Pre-registration step 0 (177Lu PSMA RLT)
Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve a PSA50 response at C2 D22 proceed to Step 1. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.
干预措施: Questionnaire Administration (Other)
Pre-registration step 0 (177Lu PSMA RLT)
Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve a PSA50 response at C2 D22 proceed to Step 1. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.
干预措施: Computed Tomography (Procedure)
Pre-registration step 0 (177Lu PSMA RLT)
Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve a PSA50 response at C2 D22 proceed to Step 1. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.
干预措施: Bone Scan (Procedure)
Pre-registration step 0 (177Lu PSMA RLT)
Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve a PSA50 response at C2 D22 proceed to Step 1. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.
干预措施: PSMA PET Scan (Procedure)
Pre-registration step 0 (177Lu PSMA RLT)
Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve a PSA50 response at C2 D22 proceed to Step 1. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.
干预措施: MRI (Procedure)
Randomization step 1 arm 1 (standard dose 177Lu PSMA RLT)
Patients receive 177Lu PSMA RLT IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial
干预措施: Lutetium Lu 177 Vipivotide Tetraxetan (Drug)
Randomization step 1 arm 2 (adaptive dose 177Lu PSMA RLT )
Starting cycle 2 day 42, patients undergo blood sample collection and PSA monitoring Q3W in the absence of disease progression or unacceptable toxicity. Patients with either an absolute PSA rise > 4 ng/dL, PSA rise > 25% above nadir, or clinical progression receive 177Lu PSMA RLT IV three weeks later. Patients then resume PSA monitoring Q3W with adaptive 177Lu PSMA RLT dosing as above for up to 4 total doses in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT, and bone scan throughout the trial and PSMA PET during screening. Patients with a history of brain metastases or with clinical indication also undergo MRI throughout the trial.
干预措施: Bone Scan (Procedure)
结局指标
主要结局
Overall survival (OS)
时间窗: Up to 5 years
Will be calculated as time from randomization until death due to any cause, censoring patients not known to have died at the time of their last follow-up. OS will be compared between the treatment arms using a stratified log rank test
Quality of life
时间窗: Up to 30 months
Will be measured using the Functional Assessment of Cancer Therapy- Prostate (FACT-P) total scores. A repeated measures mixed model will be used to evaluate the between-arm mean difference in FACT-P Total scores across the first 30 months from treatment start. A point estimate of the difference and 95% confidence interval will be reported. Results of formal hypothesis testing will only be reported if adaptive dosing is deemed noninferior to standard dosing with regards to overall survival.
次要结局
- Duration of treatment(Up to 5 years)
- Radiographic progression-free survival (rPFS)(Up to 5 years)
- Rate of Grade 3+ AEs(Up to 5 years)
- Prostate-specific antigen (PSA) response(Prior to randomization)
- Nadir PSA(Up to 5 years)
- Pain Severity(Up to 30 months)
- Quality-adjusted life years(Up to 5 years)