Docetaxel Addition in Metastatic Castrate-Sensitive Prostate Cancer (ASPIRE)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,260
- 试验地点
- 210
- 主要终点
- Overall survival (OS)
研究概览
简要总结
This phase III trial compares the effect of adding docetaxel to hormonal therapy and apalutamide versus hormonal therapy and apalutamide alone in treating patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Hormone therapy for prostate cancer, also called androgen deprivation therapy (ADT), uses surgery or drugs to lower the levels of male sex hormones in a man's body. This helps slow the growth of prostate cancer. Apalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Giving docetaxel in addition to the usual treatment of hormonal therapy and apalutamide may work better in treating patients with metastatic prostate cancer than the usual treatment alone.
详细描述
PRIMARY OBJECTIVE:
I. To determine if the addition of docetaxel to androgen deprivation therapy and apalutamide improves overall survival for men with metastatic castrate sensitive prostate cancer.
SECONDARY OBJECTIVES:
I. To determine if the addition of docetaxel to androgen deprivation therapy and apalutamide improves overall survival for men whose cancers have loss or inactivating mutations of TP53, PTEN, or RB1.
II. To determine if the addition of docetaxel to ADT plus apalutamide improves the time to radiographic progression per Prostate Cancer Working Group 3 (PCWG3) guidelines.
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
- •Documentation of disease:
- •* Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology
- •Must have had evidence of metastatic disease (American Joint Committee on Cancer [AJCC] metastasis [M]1 disease) based on conventional CT/MRI and/or bone scan. This will be defined as:
- •Bone metastases detected by CT, radionuclide technetium-99 (99Tc)- methylene bisphosphonate bone scan, or MRI as defined by PCWG3 criteria; OR
- •Non-pelvic lymph node metastases (measurable lymph nodes above the aortic bifurcation; lymph nodes are measurable if the short axis diameter is ≥ 15 mm) detected on CT or MRI as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.
- •Subjects with regional lymph node metastases only (nodes [N]1, below the aortic bifurcation) will not be eligible for the study; OR
- •Visceral or soft tissue metastases detected on CT or MRI as defined by RECIST version 1.
- •Soft tissue/visceral lesions are measurable if the long axis diameter is ≥ 10 mm
- •Evidence of metastatic disease by PSMA-PET only and not visible by CT, radionuclide bone scan, or MRI will not satisfy eligibility criteria
- •No metachronous low-volume disease (defined as recurrent metastatic disease after definitive treatment of prostate primary) and with ≤ 4 bone metastasis and no visceral metastasis on conventional imaging by CT, radionuclide 99Tc-biphosphonate bone scan, or MRI)
- •Next generation sequencing (NGS) results from any tissue based Clinical Laboratory Improvement Act (CLIA) test must be available at the time of registration. NGS from soft tissue or visceral lesion if available is preferred. NGS from bone or primary prostate will be accepted. Patients with failed NGS testing are not eligible
- •Prior treatment
- •ADT (luteinizing hormone-releasing hormone [LHRH] agonist/antagonist or orchiectomy) with or without first generation anti-androgen, or second-generation androgen receptor signaling inhibitor (ARSI) within 120 days of registration is permitted. No washout period will be needed for the first generation- androgen or ARSI prior to registration. Anti-androgen treatment is only permitted if used within 120 days of registration
- •No prior chemotherapy for prostate cancer
- •Age ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Absolute neutrophil count (ANC) ≥ 1,500/mm^3
- •Hemoglobin ≥ 9.0 g/dL
- •Platelet count ≥ 100,000/mm^3
- •Total bilirubin ≤ 1 x upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1 × ULN, subject may be eligible)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate transaminase [SGT]) ≤ 1.5 x upper limit of normal (ULN)
- •Calculated (Calc.) creatinine clearance > 30 mL/min
- •Serum potassium ≥ 3.5 mmol/L
- •Comorbid conditions
- •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- •Leptomeningeal metastases: Patients with treated leptomeningeal metastases are eligible if follow-up brain imaging 30 days after central nervous system (CNS)-directed therapy shows no evidence of progression
- •HIV: 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
- •Hepatitis B: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- •Hepatitis C: 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
- •No seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to randomization, brain arteriovenous malformation or condition requiring CNS surgery or radiation therapy)
- •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. Any condition that in the opinion of the investigator, would preclude participation in this study. Patients with stable asymptomatic deep venous thromboembolism on stable anti-coagulation will be eligible
- •Hypertension: Subjects with uncontrolled hypertension as indicated by a resting systolic blood pressure (BP) >= 160 mmHg or diastolic BP >= 100 mmHg despite medical management are not permitted to register
- •Allergies: Subjects with known hypersensitivity to any of the study drugs, or excipients in the formulation of the study drugs are not permitted to register
- •Concomitant medications
- •Chronic concomitant treatment with strong inhibitors of cytochrome P450 3A4 (CYP3A4) is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug prior to registration on the study. See Section 8.1.9 for more information
- •Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment
- •Medications known to lower the seizure threshold must be discontinued or substituted prior to study entry. See Section 8.1.9 for more information
- •Patient agrees to use a condom (even men with vasectomies) and another effective method of birth control if having sex with a woman of childbearing potential or agrees to use a condom if having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug
排除标准
- 未提供
研究组 & 干预措施
Arm 1 (ADT, apalutamide)
Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study.
干预措施: Androgen Therapy (Drug)
Arm 1 (ADT, apalutamide)
Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm 1 (ADT, apalutamide)
Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study.
干预措施: Computed Tomography (Procedure)
Arm 1 (ADT, apalutamide)
Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study.
干预措施: PSMA PET Scan (Procedure)
Arm 2 (ADT, apalutamide, docetaxel)
Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour every 21 days for up to 6 doses. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study.
干预措施: Docetaxel (Drug)
Arm 2 (ADT, apalutamide, docetaxel)
Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour every 21 days for up to 6 doses. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study.
干预措施: Apalutamide (Drug)
Arm 1 (ADT, apalutamide)
Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study.
干预措施: Bone Scan (Procedure)
Arm 1 (ADT, apalutamide)
Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study.
干预措施: Questionnaire Administration (Other)
Arm 2 (ADT, apalutamide, docetaxel)
Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour every 21 days for up to 6 doses. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study.
干预措施: Androgen Therapy (Drug)
Arm 2 (ADT, apalutamide, docetaxel)
Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour every 21 days for up to 6 doses. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study.
干预措施: Computed Tomography (Procedure)
Arm 2 (ADT, apalutamide, docetaxel)
Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour every 21 days for up to 6 doses. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm 2 (ADT, apalutamide, docetaxel)
Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour every 21 days for up to 6 doses. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study.
干预措施: Questionnaire Administration (Other)
Arm 2 (ADT, apalutamide, docetaxel)
Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour every 21 days for up to 6 doses. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm 2 (ADT, apalutamide, docetaxel)
Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour every 21 days for up to 6 doses. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study.
干预措施: PSMA PET Scan (Procedure)
Arm 1 (ADT, apalutamide)
Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study.
干预措施: Apalutamide (Drug)
Arm 1 (ADT, apalutamide)
Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm 2 (ADT, apalutamide, docetaxel)
Patients receive ADT at the discretion of the investigator and apalutamide PO QD. Cycles repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour every 21 days for up to 6 doses. Additionally, patients undergo CT scan or MRI and bone scan throughout the study. Patients may optionally undergo PSMA-PET scans and blood sample collection throughout the study.
干预措施: Bone Scan (Procedure)
结局指标
主要结局
Overall survival (OS)
时间窗: From randomization to death due to any cause, assessed up to 10 years
Will determine OS. To assess the potential OS benefit from the triplet therapy, a group sequential efficacy/futility monitoring design will be employed. The planned analyses for OS will be tested using a one-sided type 1 error rate of 0.025. An intent-to-treat approach will be used to evaluate OS between treatments. The stratified logrank test will be the primary analysis to compare OS between treatments. The Kaplan-Meier estimate will be used to evaluate the within treatment OS distributions. In addition, the proportional hazards model will be applied to assess the treatment comparison adjusting for important covariates in predicting OS.
次要结局
- Castration-resistant prostate cancer (CRPC)(Time to prostate-specific antigen progression with serum testosterone being at castrate level < 0.50 ng/mL, or the time to progression by soft tissue/visceral lesions or time to progression by bone lesions per PCWG3 guidelines, assessed up to 10 years)
- Objective response rate (ORR)(up to 10 years)
- Overall Survival (OS)(From randomization to death due to any cause, assessed up to 10 years)
- Radiographic progression(From randomization to first documentation of radiographic progressive disease or death due to any cause, assessed up to 10 years)
- Symptomatic skeletal event free survival (SSE-FS)(From randomization to first occurrence of SSE or death from any cause, assessed up to 10 years)
- Worsening of physical symptoms of disease(up to 10 years)
- Incidence of adverse events(up to 10 years)
- Radiographic progression free survival (rPFS)(From randomization to first documentation of radiographic progressive disease or death due to any cause, assessed up to 10 years)
- OS(Will determine OS in patients by the stratification factors a) timing/volume of disease 1) metachronous high volume, 2) synchronous high volume and 3) synchronous low volume metastases on conventional imaging. To assess the potential OS benefit from the)
- Prostate specific antigen (PSA) 90 response rate(At 6 weeks and 6 months)
- Time to PSA progression(From randomization to the date of PSA progression based on PCWG3 criteria, assessed up to 10 years)