Radiotherapy As an Immunological Booster in Patients with Metastatic Melanoma or Renal Cell Carcinoma Treated with High-dose Interleukin-2: Evaluation of Biomarkers of Immunologic and Therapeutic Response
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 2
- 主要终点
- immunological efficacy
研究概览
简要总结
Title: Radiotherapy as an immunological booster in patients with metastatic melanoma or renal cell carcinoma treated with High-dose Interleukin-2: evaluation of biomarkers of immunologic and therapeutic response
Phase: Proof of Principle phase II study
Study Design: Single center, open-label trial to assess the immune response and potential biomarkers predictive of response
Study Duration:
Total duration: 36 months Enrollment: 20 months Treatment: 5 months per patient Follow-up every three months
Number of Subjects:
Mini-max two-stage Simon design:
• Step 1: 7 patients enrolled
If tumor antigen-specific immune response is observed in at least 3 patients:
• Step 2: recruitment of an additional 12 patients
详细描述
Title: Radiotherapy as an immunological booster in patients with metastatic melanoma or renal cell carcinoma treated with High-dose Interleukin-2: evaluation of biomarkers of immunologic and therapeutic response
Phase: Proof of Principle phase II study
Study Design: Single center, open-label trial to assess the immune response and potential biomarkers predictive of response
Study Duration:
Total duration: 36 months Enrollment: 20 months Treatment: 5 months per patient Follow-up every three months
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
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have histologically or cytologically confirmed non resectable stage III or IV advanced melanoma or Renal Cell Carcinoma (RCC).
- •Patients must have a minimum of two lesions and one of which must be measurable, (it can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan).
- •At least one tumor lesion accessible for bioptic sampling.
- •Prior lines (maximum 4) of chemotherapy, immunotherapy or biological therapy (e.g. inhibitors of B-Raf or c-Kit, Ipilimumab, etc.) for advanced disease are allowed (patients must have finished prior treatments at least 4 weeks before the first IL2 dose);
- •Male or Female, aged >= 18 years.
- •Life expectancy of greater than 3 months.
- •ECOG performance status <=1
- •Patients must have normal organ and marrow function as defined below:
- •leukocytes >=3,500/microL
- •absolute neutrophil count >=1,500/microL
- •platelets >= 100,000/microL
- •total bilirubin within normal institutional limits
- •AST(SGOT)/ALT(SGPT) <=2.5 X institutional upper limit of normal
- •creatinine < 1,2 mg/dl
- •haemoglobin > 9.0 gm/dl
- •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
- •Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter
- •Participant is willing and able to give informed consent for participation in the study.
排除标准
- •Patient with stage I or II melanoma or RCC
- •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.
- •Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
- •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
- •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.
- •Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 5 years (except for previously treated basal cell carcinoma and in situ carcinoma of the uterine cervix);
- •HIV-positivity, whether or not symptomatic.
结局指标
主要结局
immunological efficacy
时间窗: 3 years
Determination of the immunological efficacy of the combined RT (radiotherapy)/HDIL-2 (high dose Interleukin 2) treatment in terms of ability of the treatment to enhance the proportion of circulating immune effectors specific for tumor antigens known to be expressed in RCC (Renal Cell Carcinoma) and/or melanoma
Biomarkers predictive value for treatment benefit
时间窗: 3 years
Determination of the predictive value of pretreatment biomarkers in identifying patients who will benefit from combined RT/HDIL-2 treatment
次要结局
- Toxicity from the time of their first treatment with HD 2.(3 years)
- Overall Survival(3 years)
- Response Rate(3 years)