A Phase 1 Dose Escalation Trial of Ipilimumab in Combination With CG1940 and CG8711 in Patients With Metastatic Hormone-Refractory Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Number of patients with adverse events
研究概览
简要总结
Ipilimumab, an antibody that blocks cytotoxic T-lymphocyte antigen 4, and GVAX have demonstrated anti-tumor activity in prostate cancer. Pre-clinical studies with this combination have demonstrated potent synergy. The purpose of this study is to investigate, using a phase-I 3+3 dose escalation design followed by an expansion cohort, the safety and efficacy of combined treatment with GVAX and ipilimumab in castration-resistant metastatic prostate cancer (CRPC) patients.
详细描述
A promising immunotherapeutic approach in prostate cancer is whole-cell vaccination. Irradiated allogeneic tumor cells expressing GM-CSF generate a long-lasting and specific anti-tumor immunity in preclinical models. Results from several phase I and II trials showed Prostate GVAX (GVAX) to be well tolerated and suggested improved survival. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a crucial immune checkpoint molecule that down-regulates T-cell activation and proliferation. Ipilimumab, a fully human monoclonal antibody (IgG1) that blocks CTLA-4, promotes antitumor immunity, and has been demonstrated in two phase III trials to improve overall survival in metastatic melanoma patients. Pre-clinical studies of the anti-CTLA-4 antibody in combination with GM-CSF secreting tumor cell vaccines demonstrated a potent synergy. In this phase I study the investigators examine in CRPC patients whether ipilimumab can be safely combined with GVAX. In addition, the investigators will treat an additional 16 patients at a dose level of 3•0 mg/kg to determine the safety profile and antitumor effects of GVAX and ipilimumab in patients with CRPC.
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 80 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Males age 18-80 years
- •Histologic diagnosis of adenocarcinoma of the prostate
- •Metastatic prostate cancer deemed to be unresponsive or refractory to hormone therapy
- •Detectable metastases by bone scan, CT scan or MRI
- •Two consecutive rising PSA values obtained at least two weeks apart and both obtained at least 4-6 weeks after discontinuation of hormone therapy. Second PSA value must be > 5.0 ng/mL. LHRH agonist should not be discontinued.
- •Testosterone < 50 ng/dL. Must have had orchiectomy or is currently receiving an LHRH agonist.
- •WBC > 3.0 x 109/L, ANC > 1.5 x 109/L, hemoglobin > 6.2 mmol/L, and platelets > 100 x 109/L
- •Serum creatinine < 177 umol/L Bilirubin < 1.5 times the upper limit of normal AST < 3 times the upper limit of normal
- •ECOG performance status 0-2
- •Life expectancy of at least 6 months
- •If sexually active, willing to use barrier contraception during the treatment phase of the protocol
- •The ability to understand and willingness to sign a written informed consent
排除标准
- •Transitional cell, small cell, neuroendocrine, or squamous cell prostate cancer
- •Bone pain severe enough to require routine narcotic analgesia use
- •Clinical evidence of brain metastases or history of brain metastases
- •Seropositive for HIV, Hepatitis B antigen positive and/or Hepatitis C viremic
- •Prior chemotherapy or immunotherapy for prostate cancer
- •Radiation therapy within 4 weeks of the first treatment
- •Surgery within 4 weeks of the first treatment. Must have recovered from all side effects.
- •Flutamide within 4 weeks of the first treatment Megesterol acetate (Megace), finasteride (Proscar), bicalutamide (Casodex),nilutamide, aminoglutethimide, ketoconazole or diethylstilbestrol within 6 weeks of the first treatment.
- •Systemic corticosteroid use within 4 weeks of the first treatment
- •History of autoimmune disease
- •History of another malignancy, except for the following: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, adequately treated Stage I or II cancer currently in complete remission or any other cancer that has been in complete remission for at least 5 years
研究组 & 干预措施
Ipilimumab and GVAX
干预措施: GVAX and ipilimumab (Drug)
结局指标
主要结局
Number of patients with adverse events
时间窗: 7 months
次要结局
- number of patients that have a tumor/PSA response(7 months)
- the number of patients that have activated T cells and dendritic cells as measured by FACS(7 months)
- number of patients that will develop a tumor-specific (e.g. PSMA, NY-ESO) antibody response as measured by ELISA(7 months)
研究者
A.J.M. van den Eertwegh
Dr.
Amsterdam UMC, location VUmc