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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。这是一项前瞻性I-II期研究，旨在评估HSV-tk+伐昔洛韦基因治疗联合放疗治疗既往未经治疗的前列腺癌的疗效和毒性。本研究由三个组组成（受试者人群标准见下文）。A组将包括低风险患者（具有有利的预后因素），而B组将包括高风险患者（具有不利的预后因素）。C组由经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术作为其标准治疗的一部分。HSV-tk +伐昔洛韦治疗后，将通过血清PSA水平和直肠指检的变化以及再活检时的组织学改变（如细胞凋亡、坏死、肿瘤增殖和免疫学反应的存在）评估临床反应。还采集血液样品用于评估全身免疫应答。将测量血清睾酮。此外，将对患者进行密切随访，以评估最低PSA、无PSA进展、无局部和远处进展以及总生存期。

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.