High Precision Stereotactic Radiotherapy to the Whole Prostate With Focal Boost and Varying Hormonal Therapy (HEATWAVE)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 95
- 试验地点
- 2
- 主要终点
- Percent of patients achieving prostate specific antigen (PSA) of < 0.2 ng/mL
研究概览
简要总结
This phase II trial evaluates apalutamide in combination with image-guided stereotactic body radiation therapy (SBRT) for the treatment of patients with prostate cancer. Prostate cancer usually needs the hormone testosterone to grow. Apalutamide is a hormone therapy that blocks the effect of testosterone on prostate tumor cells. This may help stop the growth of tumor cells that need testosterone to grow. Image-guided SBRT is a standard treatment for some types of prostate cancer. This treatment combines imaging of cancer within the body, with the delivery of therapeutic radiation doses produced on a linear accelerator machine. SBRT uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Combining apalutamide with image-guided SBRT may increase a prostate cancer patient's chances of achieving an extremely low prostate specific antigen response, which is an early predictor of disease cure.
详细描述
PRIMARY OBJECTIVE:
I. To assess prostate specific antigen (PSA) complete response rates in patients with unfavorable intermediate risk prostate cancer who are receiving apalutamide monotherapy in conjunction with magnetic resonance imaging stereotactic body radiotherapy with precision dose-escalation and de-escalation to involved and uninvolved areas of the prostate, respectively.
SECONDARY OBJECTIVES:
I. Assessing time to biochemical recurrence (BCR; PSA ≥ nadir PSA + 2 ng/mL) among patients initially meeting primary endpoint.
II. Assessing patient-reported genitourinary quality of life, as assessed by the Expanded Prostate Cancer Index Composite-26 (EPIC-26) survey instrument 24 months after radiotherapy completion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Confirmed diagnosis of prostate adenocarcinoma
- •Classified as having National Comprehensive Cancer Network unfavorable intermediate risk prostate cancer (i.e., [a] 2 of the following: PSA 10-20 ng/mL, clinical T category 2b-2c, or International Society of Urological Pathology [ISUP] grade group 2; [b] OR any 1 of [a] with ISUP grade group 3 disease; OR [c] any 1 of [a] with 50% or more cores on systematic biopsy showing prostate cancer)
- •Have a Decipher genomic classifier score
- •Have at least one dominant intraprostatic lesion visible on multiparametric MRI (Prostate Imaging-Reporting and Data System [PI-RADS] version 2.1 score 4 or 5)
- •Have underwent a prostate specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)
- •Have total testosterone >= 150 ng/dL
- •Adequate performance status (Eastern Cooperative Oncology Group [ECOG] 0-1)
- •Hemoglobin ≥ 9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization (at screening)
- •Platelet count ≥ 100,000 x 10^9/uL independent of transfusion and/or growth factors within 3 months prior to randomization (at screening)
- •Serum albumin ≥ 3.0 g/dL (at screening)
- •Glomerular filtration rate (GFR) ≥ 45 mL/min (at screening)
- •Serum potassium ≥ 3.5 mmol/L (at screening)
- •Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 x ULN, subject may be eligible) (at screening)
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x ULN (at screening)
- •Medications known to lower the seizure threshold (see list under prohibited medications) must be discontinued or substituted at least 4 weeks prior to study entry
排除标准
- •Any evidence of spinal cord compression (radiological or clinical)
- •Prior pelvic malignancy
- •Prior pelvic radiation
- •Concurrent malignancy other than adequately treated basal cell or squamous cell skin cancer, non-muscle invasive bladder cancer (NMIBC), or any other cancer in situ currently without evidence of recurrence or progression
- •Inability to undergo radiotherapy, or hormonal therapy
- •Primary small cell carcinoma of the prostate (prostate adenocarcinoma with neuroendocrine differentiation is allowed)
- •Inflammatory bowel disease or active collagen vascular disease
- •History of any of the following:
- •Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy)
- •Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization
- •Current evidence of any of the following:
- •Uncontrolled hypertension
- •Gastrointestinal disorder affecting absorption
- •Known active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis)
- •Any condition that in the opinion of the investigator would preclude participation in this study
- •Treatment with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, a dose reduction of the CYP2D6 substrate may be considered
- •Baseline moderate and severe hepatic impairment (Child Pugh class B & C)
研究组 & 干预措施
Treatment (apalutamide, SBRT)
Patients receive apalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 or 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo SBRT for 5 fractions over 1-2 weeks beginning on day 1 of cycle 1. Patients also undergo multiparametric MRI and collection of blood samples throughout the trial. Patients undergo PSMA-PET/CT scans during screening and follow up.
干预措施: Apalutamide (Drug)
Treatment (apalutamide, SBRT)
Patients receive apalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 or 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo SBRT for 5 fractions over 1-2 weeks beginning on day 1 of cycle 1. Patients also undergo multiparametric MRI and collection of blood samples throughout the trial. Patients undergo PSMA-PET/CT scans during screening and follow up.
干预措施: Computed Tomography (Procedure)
Treatment (apalutamide, SBRT)
Patients receive apalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 or 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo SBRT for 5 fractions over 1-2 weeks beginning on day 1 of cycle 1. Patients also undergo multiparametric MRI and collection of blood samples throughout the trial. Patients undergo PSMA-PET/CT scans during screening and follow up.
干预措施: Biospecimen Collection (Procedure)
Treatment (apalutamide, SBRT)
Patients receive apalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 or 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo SBRT for 5 fractions over 1-2 weeks beginning on day 1 of cycle 1. Patients also undergo multiparametric MRI and collection of blood samples throughout the trial. Patients undergo PSMA-PET/CT scans during screening and follow up.
干预措施: Gallium Ga 68 Gozetotide (Other)
Treatment (apalutamide, SBRT)
Patients receive apalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 or 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo SBRT for 5 fractions over 1-2 weeks beginning on day 1 of cycle 1. Patients also undergo multiparametric MRI and collection of blood samples throughout the trial. Patients undergo PSMA-PET/CT scans during screening and follow up.
干预措施: Guided Stereotactic Body Radiation Therapy (Radiation)
Treatment (apalutamide, SBRT)
Patients receive apalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 or 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo SBRT for 5 fractions over 1-2 weeks beginning on day 1 of cycle 1. Patients also undergo multiparametric MRI and collection of blood samples throughout the trial. Patients undergo PSMA-PET/CT scans during screening and follow up.
干预措施: Multiparametric Magnetic Resonance Imaging (Procedure)
Treatment (apalutamide, SBRT)
Patients receive apalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 or 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo SBRT for 5 fractions over 1-2 weeks beginning on day 1 of cycle 1. Patients also undergo multiparametric MRI and collection of blood samples throughout the trial. Patients undergo PSMA-PET/CT scans during screening and follow up.
干预措施: Positron Emission Tomography (Procedure)
Treatment (apalutamide, SBRT)
Patients receive apalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 or 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo SBRT for 5 fractions over 1-2 weeks beginning on day 1 of cycle 1. Patients also undergo multiparametric MRI and collection of blood samples throughout the trial. Patients undergo PSMA-PET/CT scans during screening and follow up.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Percent of patients achieving prostate specific antigen (PSA) of < 0.2 ng/mL
时间窗: Three months after completion of apalutamide
Will be summarized by count and percent along with the 95% confidence interval. This will then be compared to the historical control rate of 70% using a two sample z test for proportions with a one-sided p-value threshold of 0.05.
次要结局
- Time to biochemical recurrence (BCR)(We will follow patients for five years following completion of radiotherapy. Biochemical disease status will be checked every 3 months for the first year, and every 6 months thereafter.)
- Patient-reported outcomes (PROs) on the Expanded Prostate Cancer Index Composite-26 (EPIC-26) urinary domain(24 months after completion of stereotactic body radiation therapy (SBRT))
- PROs on the EPIC-26 bowel domain(24 months after completion of SBRT)
- Radiographic persistence of disease on multiparametric magnetic resonance imaging(At 6 months, 12 months, 18 months, 24 and 30 months after radiotherapy completion)
- Longitudinal PROs on the EPIC-26 questionnaire in the sexual, urinary, and bowel domains(Up to 60 months)
- Radiographic persistence of disease on prostate specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)(6 months after hormonal therapy completion)
- Physician-reported acute and late toxicities(We will follow patients for five years following completion of radiotherapy. Acute toxicity will be scored within the first 90 days after radiation. Late toxicity and patient-reported outcomes will be assessed every 3 months for the first year, and every)