Vaccination With Dendritic Cells Pulsed With Autologous Tumor Homogenate in Combination With HD-IL2 and Immunomodulating Radiotherapy in Metastatic RCC: a Phase II Trial (RENALVax-2)
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Overall Response Rate (ORR) by Immune related Response Criteria( irRC)
研究概览
简要总结
Single center, open-label Proof of Principle phase II trial to assess objective response (ORR).
Three daily doses boost radiotherapy (XRT) at 6-12 Gy to at least 1, and up to a maximum of 5, metastatic fields, will be administrated on days -4 -3 -2 or -3 -2 -1 before the first and the third cycle of vaccine+IL-2. The first day of administration of vaccine is day +1 and of IL-2 is day +2.
Treatment vaccine plus IL-2 (dose 18 MIU/m2/day in 500cc by continuous IV infusion for 72 hours) will be administered every 3 weeks up to 6 cycles.
Total duration of the trial: 36 months
- Enrolment period: 24 months
- Treatment: maximum of 6 cycles (5 months) per patient
- Follow-up every three months until patient died (follow-up until PD and only survival contacts and subsequent therapy for metastatic disease after PD).
详细描述
Vaccination with dendritic cells pulsed with autologous tumor homogenate in combination with HD-IL2 and immunomodulating radiotherapy in metastatic RCC: a phase II trial Proof of Principle phase II study Study Design Single center, open-label trial to assess response rate Study Duration Total duration: 36 months Enrollment: 24 months Treatment: 5 months per patient Follow-up every three months Primary objectives: Overall Response Rate (ORR) by irRC
Secondary end points:
- Toxicity
- Overall Survival
- Duration of response
- PFS
- ORR by RECIST 1.1
- Prognostic and predictive marker response
- Immunological response Study Product, Dose, Route, Regimen and duration of administration Three daily doses boost radiotherapy (XRT) at 6-12 Gy to at least 1, and up to a maximum of 5, metastatic fields, will be administrated on days -4 -3 -2 or -3 -2 -1 before the first and the third cycle of vaccine+IL-2. The first day of administration of vaccine is day +1 and of IL-2 is day +2.
The intradermal autologous dendritic cell vaccine loaded with autologous tumor homogenate plus IL-2 (dose 18 MIU/m2/day in 500cc by continuous IV infusion for 72 hours) will be administered every 3 weeks up to 6 cycles.
Statistical Methodology
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed Written Informed Consent: patients must be willing and able to give written informed consent, that have to be given before starting of screening procedure.
- •Availability of autologous tumor tissue fulfilling acceptance criteria prescribed by the "Product Specification File".
- •Patients must have histologically or cytologically confirmed RCC (all histology types except for urothelial cancer);
- •Patients must have stage IV disease in progression after at least 1 TKI and/or antiangiogenetic and/or mTOR inhibitors therapy (patients must have finished prior treatments at least 4 weeks before the first IL2 dose)
- •Patients must have at least one measurable lesion, according to the irRC response criteria (see section 8 ), after asportation of tumor tissue for vaccine preparation. The tumor lesions that will be irradiated are excluded for response evaluation.
- •Life expectancy of greater than 3 months.
- •ECOG performance status 0-1
- •Patients must have organ and marrow function as defined below:
- •leukocytes >4000/µL
- •absolute neutrophil count >1,500/µL
- •platelets >100,000/µL
- •total bilirubin within normal institutional limits
- •AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal
- •creatinine < 1.5 mg/dl
- •haemoglobin >8.0 gm/dl
- •hematocrit <30%
- •ECG and echocardiogram within normal institutional limits
- •Pulmonary function tests within normal institutional limits (to be performed only in patients with lung metastases or history of impaired lung function)
- •No contraindication for the use of vasopressor agents
- •Negative screening tests for HIV, HBV HCV and syphilis not older than 30 days before performing any of the GMP-regulated activities required (leukapheresis, collection of tumor biopsies to be used for tumor homogenate preparation);
- •Men and women aged > 18 years.
- •Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up 8 weeks after the study, in order to minimize the risk of pregnancy;
- •Patients must have normal organ and marrow function according to clinical practice.
排除标准
- •Patients who have positive tests to HCV, HBV, HIV, or syphilis (specific blood testing must be performed within 30 days before any GMP-regulated activity (leukapheresis and collection of tumor biopsies to be used for tumor homogenate preparation).
- •Patients who did not have prior lines of systemic therapy for advanced disease.
- •Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements (on physician's judgment).
- •Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 3 years (except for previously treated basal cell carcinoma and in situ carcinoma of the uterine cervix);
- •Patients who have had chemotherapy or radiotherapy or immunotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- •Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to IL-2 or other agents used in the study.
- •Any autoimmune disease which could be exacerbated by IL-2
- •A medical illness requiring chronic treatments with corticosteroids or other immunosuppressive agents
- •A history of significant cardiovascular disease, including myocardial infarction, congestive heart failure, primary cardiac arrhythmias, angina pectoris or cerebrovascular accident
- •HIV-positivity, whether or not symptomatic
- •Any contraindication to undergo leukapheresis as evaluated by transfusionist (e.g. severe anemia, piastrinopenia, oral anticoagulant therapy) or to undergo surgery.
研究组 & 干预措施
study treatment
boost radiotherapy (XRT) plus intradermal autologous dendritic cell vaccine loaded with autologous tumor homogenate (Autologous DC vaccine) plus High-Dose IL-2
干预措施: boost radiotherapy (XRT) (Radiation)
study treatment
boost radiotherapy (XRT) plus intradermal autologous dendritic cell vaccine loaded with autologous tumor homogenate (Autologous DC vaccine) plus High-Dose IL-2
干预措施: Autologous DC vaccine (Biological)
study treatment
boost radiotherapy (XRT) plus intradermal autologous dendritic cell vaccine loaded with autologous tumor homogenate (Autologous DC vaccine) plus High-Dose IL-2
干预措施: High-Dose IL-2 (Drug)
结局指标
主要结局
Overall Response Rate (ORR) by Immune related Response Criteria( irRC)
时间窗: up to 24 months
The analysis will be performed on an intention to treat population, i.e. all patients having received at least 2 cycles of therapy.
次要结局
- Overall survival (OS)(up to 24 months)
- Duration of response(up to 24 months)
- Progression free survival(up to 24 months)
- Immunologic efficacy(up to 24 months)
- Adverse events evaluation(up to 24 months)