Hormone Therapy With or Without Definitive Radiotherapy in Metastatic Prostate Cancer
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Disease progression-free survival
研究概览
简要总结
PART I
Hormone therapy with or without definitive radiotherapy in metastatic prostate cancer
The goal of this clinical study PART I is to determine impact of radiotherapy treatment in combination with standard androgen deprivation therapy comparing with androgen deprivation therapy alone at controlling metastatic prostate cancer. The primary objective: to determine disease progression free survival in man with metastatic (M1) prostate cancer (PC) undergoing androgen deprivation therapy with or without definitive radiotherapy of the primary tumor.The secondary objective: to determine disease progression (local, bone marrow, visceral) in men with metastatic prostate cancer (M1PC) undergoing systemic therapy with/without definitive radiotherapy of the primary tumor, to determine expression in number of genes analysed 8: 2 housekeeping genes; integrin subunits αv, β3, β5, α4β1 ; 3 EMT markers N-cadherin, E-cadherin, vimentin before radiotherapy, after radiotherapy and at the time of the disease progression , to determine plasma serotonin (5HT, 5 hydroxytryptamine). Subgroup analysis in locally advanced prostate cancer (serves as a control group for integrins analysis): to determine expression in number of genes analysed 8: 2 housekeeping genes; integrin subunits αv, β3, β5, α4β1 ; 3 epithelial-mesenchymal transition (EMT) markers N-cadherin, E-cadherin, vimentin before radiotherapy, after radiotherapy and at the time of the disease progression.
PART II
Identification of genetic determinants of disease progression and castrate resistance in metastatic prostate cancer.
The goal of this clinical study PART II is to assess feasibility of genomic testing in the multidisciplinary clinical management of metastatic prostate cancer, to gain insight in specific genomic signature(s) of progressive metastatic prostate cancer in the natural course of disease spanning from primary tumor to metastases, to test if 'treatment selection' and/or 'treatment adaptation' as means of evolutionary pressures represent the mechanistic models of castrate resistance and ultimate treatment failure following course of androgen deprivation therapy (ADT).
详细描述
PART I
Standard therapy for men presenting with metastatic prostate cancer is initiation of androgen suppression, whereas radiotherapy or surgery are currently used only in palliative efforts to relieve symptoms of bleeding, pain, or obstruction. The integration of radiation to the prostate has not been prospectively explored in the metastatic setting.
Although there is no study evidence on the effect of local therapy on outcomes in metastatic prostate cancer, there are hypotheses-generating data that support this concept as an appropriate question to be answered in the context of a randomized trial. Prospective data show improved outcomes for men with locally advanced prostate cancer undergoing multimodality therapy with androgen-deprivation therapy (ADT) or radiation therapy (RT) compared to systemic monotherapy alone . Continuing on the spectrum of the disease, recent data presented at the 2014 European Society for Medical Oncology Annual Meeting showed improved failure-free survival in men with clinically positive lymph nodes receiving combination ADT and RT versus ADT alone.
Several population-based studies have shown improved overall survival in men with metastatic disease undergoing combination local and systemic therapy versus standard-of-care systemic therapy alone .
Previous studies showed that initial event at a metastatic site is not the arrival of tumor cells but rather the clustering of bone marrow-derived cells . This cells make the local microenvironment of the secondary organ more receptive to tumor cell colonization and are stimulated by endocrine factors released by the primary tumor . According to this, local treatment of the primary tumor could postpone the formation and the growth of distant metastases; metastatic prostate cancer may represent a heterogeneous population and the impact of local treatment on disease progression on survival might be influenced by primary tumor characteristics.
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 80 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male patients with newly diagnosed metastatic prostate cancer
- •Androgen dependent disease measured by declining PSA
- •ECOG PS 0 or 1
- •Life-expectancy based on comorbid conditions >2 years
- •Ability to understand and willingness to sign informed consent
- •Must be candidate for radiation therapy
排除标准
- •Poor performance status, history of connective tissue disorder
- •Psychiatric or medical conditions which would not allow the patient to undergo the proposed treatment safely
- •Known brain metastasis
研究组 & 干预措施
pelvic radiotherapy
long-term hormonal therapy (LHRH agonist and/or antiandrogens) plus radiotherapy to the pelvis and prostate
干预措施: Radiotherapy to the pelvis (Radiation)
pelvic radiotherapy
long-term hormonal therapy (LHRH agonist and/or antiandrogens) plus radiotherapy to the pelvis and prostate
干预措施: Hormonal therapy (LHRH agonist and/or antiandrogens) (Drug)
No pelvic radiotherapy
long-term hormonal therapy ( LHRH agonist and/or antiandrogens) alone
干预措施: Hormonal therapy (LHRH agonist and/or antiandrogens) (Drug)
结局指标
主要结局
Disease progression-free survival
时间窗: 4 years
Time to prostate specific antigen (PSA) progression
次要结局
- Prostate, bone marrow and viscera progression-free survival(4 years)
- Expression of integrins(4 years)
研究者
Ana Frobe
MD, PhD, Prof.
University Hospital "Sestre Milosrdnice"