Bipolar Androgen Therapy in Metastatic Castration-Resistant Prostate Cancer (mCRPC)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Androgen receptor (AR) activity
研究概览
简要总结
This phase I trial tests the change in androgen receptor sensitivity, side effects and effectiveness of bipolar androgen therapy, using testosterone, in patients with castration resistant prostate cancer that has spread to other places is the body (metastatic). Bipolar androgen therapy is the regulation of testosterone between castration levels (lower than what would be normally present) and supraphysiological levels (amounts greater than normally found in the body). This may suppress cancer cell growth, which reduces prostate-specific antigen (PSA) levels and may delay cancer progression.
详细描述
PRIMARY OBJECTIVE:
I. To determine the influence of bipolar androgen therapy (BAT) on androgen receptor (AR) activity in patients with metastatic castration-resistant prostate cancer (mCRPC).
SECONDARY OBJECTIVES:
- To determine the clinical efficacy and safety of BAT in patients with mCRPC.
- To determine the change in fatigue and quality of life in patients receiving BAT.
OUTLINE:
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
- •Age ≥ 18 years of age
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
- •Histologically confirmed carcinoma of the prostate
- •Progressing on continuous androgen ablative therapy (either surgical castration or LHRH agonist)
- •Documented castrate level of blood testosterone (< 50 ng/dL)
- •Patients must have progressed on prior treatment with at least one Androgen Receptor Signaling Inhibitors (ARSI) (by prostate specific antigen [PSA] criteria or radiographically)
- •Have biopsiable disease (a fresh biopsy is not required at baseline if adequate archival tissue is available)
- •Absolute neutrophil count: ≥1,200/µL
- •Platelets: ≥ 100,000/µL
- •Total bilirubin: ≤ 1.2 x institutional upper limit of normal (ULN)
- •Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/ Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]): ≤ 3 × institutional ULN
- •Creatinine clearance (CrCl) > 50 mL/min (Cockcroft-Gault equation)
- •Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present
- •Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- •Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
排除标准
- •Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- •Greater than 5 sites of visceral disease in lung or liver (nonspecific lung nodules ≤ 1 cm in diameter is permitted)
- •Evidence of disease in sites or extent that, in the opinion of the investigator, would put the patient at risk from therapy with testosterone (e.g., femoral metastases with concern over fracture risk, spinal metastases with concern over spinal cord compression, lymph node disease with concern for ureteral obstruction)
- •Active uncontrolled infection, including known history of acquired immunodeficiency syndrome (AIDS) or hepatitis B or C
- •Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule
- •Prior history of a thromboembolic event within the last 12 months and not currently on systemic anticoagulation
- •Hematocrit > 50%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure (per Endocrine Society Clinical Practice Guidelines)
- •Evidence of serious and/or unstable pre-existing medical, psychiatric, or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study
- •Known allergy to testosterone cypionate or any of its excipients
- •Unwilling or unable to follow protocol requirements
- •Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug
研究组 & 干预措施
Treatment (Bipolar androgen therapy)
Patients receive testosterone IM on day 1 of each cycle. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also continue to receive standard of care leuprolide acetate SC per their standard schedule. Patients undergo CT scan, bone scan and may undergo MRI and tumor biopsy throughout the study.
干预措施: Leuprolide Acetate (Drug)
Treatment (Bipolar androgen therapy)
Patients receive testosterone IM on day 1 of each cycle. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also continue to receive standard of care leuprolide acetate SC per their standard schedule. Patients undergo CT scan, bone scan and may undergo MRI and tumor biopsy throughout the study.
干预措施: Testosterone Cypionate (Drug)
Treatment (Bipolar androgen therapy)
Patients receive testosterone IM on day 1 of each cycle. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also continue to receive standard of care leuprolide acetate SC per their standard schedule. Patients undergo CT scan, bone scan and may undergo MRI and tumor biopsy throughout the study.
干预措施: Survey Administration (Other)
Treatment (Bipolar androgen therapy)
Patients receive testosterone IM on day 1 of each cycle. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also continue to receive standard of care leuprolide acetate SC per their standard schedule. Patients undergo CT scan, bone scan and may undergo MRI and tumor biopsy throughout the study.
干预措施: Biopsy (Procedure)
Treatment (Bipolar androgen therapy)
Patients receive testosterone IM on day 1 of each cycle. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also continue to receive standard of care leuprolide acetate SC per their standard schedule. Patients undergo CT scan, bone scan and may undergo MRI and tumor biopsy throughout the study.
干预措施: Bone Scan (Procedure)
Treatment (Bipolar androgen therapy)
Patients receive testosterone IM on day 1 of each cycle. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also continue to receive standard of care leuprolide acetate SC per their standard schedule. Patients undergo CT scan, bone scan and may undergo MRI and tumor biopsy throughout the study.
干预措施: Computed Tomography (Procedure)
Treatment (Bipolar androgen therapy)
Patients receive testosterone IM on day 1 of each cycle. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also continue to receive standard of care leuprolide acetate SC per their standard schedule. Patients undergo CT scan, bone scan and may undergo MRI and tumor biopsy throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
结局指标
主要结局
Androgen receptor (AR) activity
时间窗: Up to 2 years after end of treatment/progression
Assessed with spatial transcriptomic profiling using the well-validated Nelson 10 genes signature AR score. Will be summarized by timepoint using the mean and standard deviation, and graphically using dot-plots. The mean pre/post-intervention levels will be compared using a one-sided paired t-test (expected increase); with the effect summarized using the mean difference and fold change.
次要结局
- Incidence of adverse events(Up to 30 days after end of treatment or progression)
- Incidence of serious adverse events(Up to 30 days after end of treatment or progression)
- Prostate specific antigen (PSA) 50(Up to 2 years after end of treatment/progression)
- Measurable disease response(Up to 2 years after end of treatment/progression)
- Progression free survival(From day 1 of treatment to the date when the first site of disease is found to progress, assessed up to 2 years after end of treatment/progression)
- Overall survival(From the time of initiation of treatment until death from any cause, assessed up to 2 years after end of treatment/progression)
- Assess Quality of life(Up to 2 years after end of treatment/progression)
- Assess Quality of Life(Up to 2 years after end of treatment/progression)
- Assess Fatigue(Up to 2 years after end of treatment/progression)
- Assess change in Fatigue(Up to 2 years after end of treatment/progression)