A Pilot Study of Rituximab Neoadjuvant Therapy in Patients With High Risk Prostate Cancer Scheduled to Undergo Radical Prostatectomy
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- B-cell Density Stained Area
研究概览
简要总结
There is now substantial evidence that B cells are recruited into prostate cancers by CXCL13 released by the tumor cells. B cells release lymphotoxin which drives malignant cell proliferation through the NFkB pathway. This is a pilot trial in 18 patients to determine whether depletion of B cells by rituximab will result in a decrease in the extent of B cell infiltration of the prostatic cancer. The extent of infiltration in the diagnostic biopsy will be compared to that in the prostatectomy samples following administration of 4 weekly doses of rituximab.
详细描述
This is an open label, single institution, pilot study of rituximab neoadjuvant therapy in patients with high risk prostate cancer scheduled to undergo radical prostatectomy. Prior to prostatectomy, patients will receive one treatment cycle (28 days) of rituximab 375 mg/m2 intravenously once weekly. Patients will be scheduled to undergo radical prostatectomy within two weeks of completing study treatment. Tissue from prostatectomy will be used for immunohistochemistry (IHC) staining of pharmacodynamic markers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Ability to understand and provide written informed consent.
- •Patient has EITHER:
- •A Kattan nomogram predicted probability of being disease free 5 years after surgery of < 60%, OR
- •A Gleason sum ≥
- •Indicated for radical prostatectomy.
- •Note: candidates for radical prostatectomy are still eligible even if they have a history of deep venous thrombosis, pulmonary embolism, and/or cerebrovascular accident or currently requiring systemic anticoagulation.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Appendix A).
- •Males aged ≥ 18 years.
- •Adequate organ function as defined below measured within 21 days of study entry:
- •Hematology:
- •Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
- •Platelet count ≥ 100 x 109/L
- •Hemoglobin ≥ 9.0 g/dL
- •White blood cell (WBC) count ≥ 3.0 x 109/L
- •Biochemistry:
- •Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamate pyruvate transaminase (ALT/SGPT) ≤ 2 x institution's upper limit of normal (ULN)
- •Total bilirubin <1.5 times ULN
- •Serum creatinine and blood urea nitrogen (BUN)<1.5 times ULN
- •Na, K Cl, carbon dioxide (CO2), Ca, phosphate (PO4) within institutional limits
- •Available prostate biopsy specimen which is evaluable for B lymphocyte count.
排除标准
- •Received prior treatment for prostatic adenocarcinoma including prior surgery (excluding TURP), radiation therapy, or chemotherapy.
- •Current or past use of investigational agents within 4 weeks of study enrollment.
- •Evidence of metastatic disease on cross sectional imaging or bone scan.
- •History of hepatitis B or C, hepatitis immunodeficiency virus (HIV), tuberculosis or a chronic infection of any type.
- •Positive test results for chronic hepatitis B infection (defined as positive HBsAg serology).
- •Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology testing).
研究组 & 干预措施
rituximab
Rituximab will be administered intravenously at a dose of 375 mg/m2 of body surface area once per week for 4 weeks (Days 1, 8, 15, and 22 of a 28-day cycle).
干预措施: rituximab (Drug)
结局指标
主要结局
B-cell Density Stained Area
时间窗: 1 treatment cycle (28 days)
Immunohistochemical staining of serial prostatectomy sections to measure the density of CD20+ B-cells as stained area (mm\^2/mm\^2)
次要结局
- Prostate-specific Antigen (PSA)(from Day 1 to Day 29)
- Change in Tumor B-cell Stained Area(from Day 1 to Day 29)
- Tumor CD3+ T-cell Stained Area(from Day 1 to Day 29)
研究者
Christopher Kane
Professor
University of California, San Diego