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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一项前瞻性I-II期研究，旨在评估HSV-tk+ valacyclovir基因治疗联合放疗治疗未经治疗的前列腺癌的疗效和毒性。本研究由三组组成（受试者总体标准见下文）。A组为低危患者（预后因素有利），B组为高危患者（预后因素不利）。C组由病理证实的髂淋巴结转移（D1期）患者组成。B组和C组患者将接受新辅助雄激素消融作为其标准治疗的一部分。通过血清PSA水平和直肠指检的变化以及再活检的组织学改变（如细胞凋亡、坏死、肿瘤增殖和免疫反应）来评估临床反应，将在HSV-tk + valacyclovir治疗后进行评估。血液样本也被用来评估全身免疫反应。测定血清睾酮。此外，将密切跟踪患者以评估PSA最低点、PSA进展自由、局部和远处进展自由以及总生存期。

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.