Investigating the Effect of Testosterone Replacement Therapy Among Hypogonadal Men With Localized Prostate Cancer on Active Surveillance
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 600
- 试验地点
- 1
- 主要终点
- Gleason grade progression
研究概览
简要总结
This phase IV trial studies the effects of testosterone replacement therapy (TRT) on treatment outcomes in hypogonadal men with prostate cancer that has not spread to other parts of the body (localized) and who are on active surveillance (AS). AS in prostate cancer involves closely watching the patient's condition through regular physical exams and blood tests, but not giving treatment unless there are changes in test results. It can be a practical alternative to treatment in localized prostate cancer. Hypogonadal men have low testosterone associated with symptoms such as low libido and erectile problems. TRT can be used to treat hypogonadism by increasing testosterone levels, which may improve associated symptoms. TRT is often not used in men with prostate cancer due to concerns it may lead to the cancer growing or spreading. This may lead hypogonadal men to have a poor quality of life or to discontinue AS. TRT may improve treatment and quality of life outcomes in hypogonadal men with localized prostate cancer on active surveillance.
详细描述
PRIMARY OBJECTIVES:
I. To investigate the impact of TRT on Gleason grade progression in hypogonadal men with localized prostate cancer on active surveillance, and the association between TRT and the likelihood of discontinuation of active surveillance in the same population.
II. To assess the impact of TRT on the quality of life, including changes in the International Prostate Symptom Score (IPSS) and the association with sexual health measured by the Sexual Health Inventory for Men (SHIM), in hypogonadal men with localized prostate cancer on active surveillance.
SECONDARY OBJECTIVES:
I. To examine the influence of TRT on radiographic progression in hypogonadal men with localized prostate cancer on active surveillance, by assessing changes in the size of abnormal magnetic resonance imaging (MRI) lesions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Men aged ≥ 18 years
- •Men with localized prostate cancer are eligible for active surveillance (National Comprehensive Cancer Network [NCCN] very low, low, and intermediate favorable risk group)
- •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
- •Patients with NCCN intermediate unfavorable, high risk, or very high-risk localized prostate cancer
- •For men being considered for Group 2 (TRT), Patients with contraindications to TRT, which include,
- •Locally advanced or metastatic prostate cancer
- •Male breast cancer
- •Men with an active desire to have children
- •Hematocrit levels > 54% or baseline hematocrit of 48-50%
- •Uncontrolled or poorly controlled congestive heart failure
- •IPSS (International Prostate Symptom Score) score > 19
- •Family history of venous thromboembolism
- •Unwilling or unable to follow protocol requirements
- •Any condition which in the investigator's opinion deems the participant an unsuitable candidate to participate in the study
研究组 & 干预措施
Group 1 (AS)
Patients with normal testosterone level undergo standard AS for up to 5 years in the absence of disease progression. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.
干预措施: Magnetic Resonance Imaging (Procedure)
Group 1 (AS)
Patients with normal testosterone level undergo standard AS for up to 5 years in the absence of disease progression. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.
干预措施: Biopsy of Prostate (Procedure)
Group 1 (AS)
Patients with normal testosterone level undergo standard AS for up to 5 years in the absence of disease progression. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.
干预措施: Biospecimen Collection (Procedure)
Group 1 (AS)
Patients with normal testosterone level undergo standard AS for up to 5 years in the absence of disease progression. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.
干预措施: Patient Observation (Other)
Group 2 (TRT, AS)
Patients with low testosterone level associated with hypogonadal symptoms and willing to receive TRT receive testosterone per treating physician discretion via injection, gel, lotion, or transdermal patch and undergo standard AS for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.
干预措施: Questionnaire Administration (Other)
Group 3 (AS)
Patients with low testosterone level with no symptoms, or low testosterone level associated with hypogonadal symptoms but declined TRT undergo standard AS for up to 5 years in the absence of disease progression. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.
干预措施: Biopsy of Prostate (Procedure)
Group 3 (AS)
Patients with low testosterone level with no symptoms, or low testosterone level associated with hypogonadal symptoms but declined TRT undergo standard AS for up to 5 years in the absence of disease progression. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.
干预措施: Biospecimen Collection (Procedure)
Group 3 (AS)
Patients with low testosterone level with no symptoms, or low testosterone level associated with hypogonadal symptoms but declined TRT undergo standard AS for up to 5 years in the absence of disease progression. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.
干预措施: Magnetic Resonance Imaging (Procedure)
Group 2 (TRT, AS)
Patients with low testosterone level associated with hypogonadal symptoms and willing to receive TRT receive testosterone per treating physician discretion via injection, gel, lotion, or transdermal patch and undergo standard AS for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.
干预措施: Therapeutic Testosterone (Drug)
Group 1 (AS)
Patients with normal testosterone level undergo standard AS for up to 5 years in the absence of disease progression. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.
干预措施: Questionnaire Administration (Other)
Group 2 (TRT, AS)
Patients with low testosterone level associated with hypogonadal symptoms and willing to receive TRT receive testosterone per treating physician discretion via injection, gel, lotion, or transdermal patch and undergo standard AS for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.
干预措施: Biopsy of Prostate (Procedure)
Group 2 (TRT, AS)
Patients with low testosterone level associated with hypogonadal symptoms and willing to receive TRT receive testosterone per treating physician discretion via injection, gel, lotion, or transdermal patch and undergo standard AS for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.
干预措施: Biospecimen Collection (Procedure)
Group 2 (TRT, AS)
Patients with low testosterone level associated with hypogonadal symptoms and willing to receive TRT receive testosterone per treating physician discretion via injection, gel, lotion, or transdermal patch and undergo standard AS for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.
干预措施: Magnetic Resonance Imaging (Procedure)
Group 2 (TRT, AS)
Patients with low testosterone level associated with hypogonadal symptoms and willing to receive TRT receive testosterone per treating physician discretion via injection, gel, lotion, or transdermal patch and undergo standard AS for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.
干预措施: Patient Observation (Other)
Group 3 (AS)
Patients with low testosterone level with no symptoms, or low testosterone level associated with hypogonadal symptoms but declined TRT undergo standard AS for up to 5 years in the absence of disease progression. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.
干预措施: Patient Observation (Other)
Group 3 (AS)
Patients with low testosterone level with no symptoms, or low testosterone level associated with hypogonadal symptoms but declined TRT undergo standard AS for up to 5 years in the absence of disease progression. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Gleason grade progression
时间窗: From start of active surveillance until any progression in primary, secondary, or a combination of Gleason grades, definitive treatment, or last follow-up, assessed up to 5 years
The Gleason grade progression will be summarized by group using standard Kaplan-Meier methods, where estimates of the median or specified rates will be obtained. Comparisons will be made between groups using the log-rank test. As exploratory analyses, Cox regression models may be considered to adjust for relevant demographic or clinical confounders. The Bonferroni method will be used to control the family-wise error rate at 0.10.
Discontinuation of active surveillance
时间窗: From start of active surveillance until discontinuation of active surveillance due to any cause or last follow-up, assessed up to 5 years
The discontinuation of active surveillance will be summarized by group using standard Kaplan-Meier methods, where estimates of the median or specified rates will be obtained. Comparisons will be made between groups using the log-rank test. As exploratory analyses, Cox regression models may be considered to adjust for relevant demographic or clinical confounders. The Bonferroni method will be used to control the family-wise error rate at 0.10.
International Prostate Symptom Score (Quality-of-life)
时间窗: Up to 5 years
Will be modeled as a function of group, timepoint, their two-way interaction, and a random subject effect using linear mixed models. Tests about the appropriate contrasts of model estimates will be used to compare mean changes in quality of life between groups at specified timepoints. All model assumptions will be verified graphically, and transformations applied as appropriate. As exploratory analyses, additional models may be considered to adjust for relevant demographic or clinical confounders. The Bonferroni method will be used to control the family-wise error rate at 0.10.
Sexual Health Inventory for Men score (Quality-of-life)
时间窗: Up to 5 years
Will be modeled as a function of group, timepoint, their two-way interaction, and a random subject effect using linear mixed models. Tests about the appropriate contrasts of model estimates will be used to compare mean changes in quality of life between groups at specified timepoints. All model assumptions will be verified graphically, and transformations applied as appropriate. As exploratory analyses, additional models may be considered to adjust for relevant demographic or clinical confounders. The Bonferroni method will be used to control the family-wise error rate at 0.10.
次要结局
- Radiographic progression(From start of active surveillance until radiographic progression, definitive treatment, or last follow-up, assessed up to 5 years)
- Incidence of TRT-related complications(Up to 5 years)
- TRT discontinuation(Up to 5 years)
- Incidence of testosterone replacement therapy (TRT)-related adverse events(Up to 5 years)
- Biochemical progression(From the start of active surveillance until prostate specific antigen (PSA) progression, definitive treatment, or last follow-up, assessed up to 5 years)