PHASE I-II STUDY ON HSV-TK GENE THERAPY + RADIOTHERAPY FOR PROSTATE CANCER

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这是一项前瞻性的I-II期研究，旨在评估HSV-tk+万乃洛韦基因治疗联合放射治疗在未经治疗的前列腺癌中的疗效和毒性。这项研究由三个部分组成(受试者人口标准见下文)。A组将包括低风险患者(具有有利的预后因素)，而B组将包括高危患者(具有不利的预后因素)。C组包括经病理证实为髂骨淋巴结转移(D1期)的患者。B组和C组患者将接受新辅助雄激素消融，作为其标准护理的一部分。在HSV-tk+万乃洛韦治疗后，将通过血清PSA水平和直肠指诊的变化以及再次活检时的组织学变化(如细胞凋亡、坏死、肿瘤增殖和免疫反应)来评估临床反应。血液样本也被用于评估全身免疫反应。将测量血清睾丸素。此外，还将密切跟踪患者以评估最低PSA、无PSA进展、无局部和远处进展以及总存活率。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a prospective phase I-II study to assess the efficacy and toxicity of HSV-tk+ valacyclovir gene therapy in combination with radiotherapy in previously untreated prostate cancer. This study is comprised of three arms (see below for subject population criteria). Arm A will include low risk patients (with favorable prognostic factors) while arm B will have high risk patients (with unfavorable prognostic factors). Arm C is comprised of patients with pathologic proven iliac lymph node metastasis (Stage D1). Arms B and C patients will receive neoadjuvant androgen ablation as part of their standard of care. Clinical response as evaluated by changes in serum PSA level and digital rectal examination as well as by histological alterations on re-biopsy such as the presence of apoptosis, necrosis, tumor proliferation and immunologic response, will be assessed following HSV-tk + valacyclovir treatment. Blood samples are also taken for assessment of systemic immunological response. Serum testosterone will be measured. Additionally, patients will be followed closely to assess nadir PSA, freedom from PSA-progression, and freedom from local and distant progression and overall survival.