The High-Dose Aldesleukin (IL-2) "Select" Trial: A Trial Designed to Prospectively Validate Predictive Models of Response to High Dose IL-2 Treatment in Patients With Metastatic Renal Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 123
- 试验地点
- 1
- 主要终点
- Objective Response in ISM Good Risk Group
研究概览
简要总结
High-dose interleukin 2 (Proleukin, Novartis) (IL-2) is approved by the U.S Food and Drug Administration (FDA) for the treatment of metastatic kidney cancer and is a standard treatment of this disease. At the present time, IL-2 is the only therapy for kidney cancer that can produce a remission of disease that lasts after treatment is completed. However, most patients who receive IL-2 do not benefit and all patients experience potentially dangerous side effects.
Recent research has suggested that certain patients may respond better to IL-2 than others. The Cytokine Working Group is currently conducting a clinical trial that aims to identify and confirm this research and narrow the application of IL-2 to those patients most likely to benefit.
详细描述
OBJECTIVES:
Primary
- To determine, in a prospective fashion, if the response rate to high-dose IL-2 for patients with metastatic renal cell carcinoma and "good" pathologic predictive features is significantly higher than a historical, unselected patient population.
Secondary
- To determine, in a prospective fashion, the response rate to high-dose IL-2 for patients with metastatic renal cell carcinoma and "poor" pathologic predictive features and to compare this response rate to the response rate of patients with "good" pathologic predictive features.
- To determine if components of other predictive and prognostic models (e.g MSKCI or UCLA criteria) can help to further define the optimal population to receive high-dose IL2 for metastatic renal cell carcinoma.
- To identify features of the baseline immune function (arginine, arginase, T cell zeta chain) of patients with metastatic renal cell carcinoma that are associated with response to high-dose IL-2.
- To identify new proteins or patterns of gene expression that might be associated with high-dose IL-2 responsiveness in order to further narrow the application of IL-2 therapy to those who will benefit the most.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have histologically confirmed renal cell carcinoma that is metastatic or unresectable.
- •If patients have measurable disease restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology.
- •Patients must provide access to tissue blocks containing adequate tumor for interpretation and analysis.
- •Patients must have measurable disease.
- •Patients must have good performance status (ECOG 0 or 1; Karnofsky PS 100-80%).
- •Patients must have adequate organ function.
- •Patients must have no contraindication of vasopressor agents.
- •Patients must be ≥ 18 years of age.
排除标准
- •Patients who have received systemic therapy for metastatic disease.
- •Patients with organ allografts.
- •Patients who require or are likely to require systemic corticosteroid therapy for intercurrent illness.
- •Patients with any significant medical disease other than the malignancy (e.g. COPD, patients with ascites or pleural effusions), which in the opinion of the investigator would significantly increase the risk of immunotherapy.
- •Patients with a history of another malignancy within the past 5 years other than surgically cured non-melanoma skin cancer, carcinoma-in-situ or Stage I carcinoma of the cervix.
研究组 & 干预措施
HD IL2
Participants received high-dose (HD) IL2, 600,000 IU/kg/dose (Prometheus Laboratories Inc.) i.v. every 8 hours for 5 days (maximum of 14 doses) beginning on day 1 and again on day 15. One course generally consisted of 5 days of treatment, 9 days of rest, 5 more days of treatment, and 9 weeks of rest, followed by up to two additional courses of HD IL2 for patients who benefited and tolerated most of the planned IL2 doses. A treatment delay of up to 4 weeks was allowed for resolution of side effects between courses. Patients were eligible to receive a maximum of three courses of treatment.
干预措施: HD IL2 (Drug)
结局指标
主要结局
Objective Response in ISM Good Risk Group
时间窗: Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).
The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on World Health Organization (WHO) criteria. \[Miller et al. Cancer 1981\] Per WHO, evaluation of tumor measurements of measurable lesions centers on the percent change from baseline in the sum of the perpendicular diameters. Complete Response (CR) is disappearance of all clinical and laboratory evidence of disease; Partial Response (PR) is a \>/= 50% decrease. PR status also requires no simultaneous increase in the size of any metastatic lesion, absence of one or more new metastatic lesions and/or unequivocal progression of existing non-target lesions. CR and PR status needs confirmation within 4 weeks. Response status was determined by investigator assessment of radiographs.
次要结局
- Objective Response Rate in ISM Poor Risk Group(Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).)
- Objective Response Rate (Independent Assessment)(Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).)
- Overall Survival(Participants were followed for survival up to 7 years.)
- Objective Response Rate by CA-9 SNP(Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).)
- Progression-Free Survival(Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Long-term follow-up occurred every 3 m for 2 yrs, semi-annually for yr 3 and annually for yrs 4 and 5. Median survival follow-up was X months (95% CI: ).)
- 3-Year Progression-Free Survival Rate(Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Long-term follow-up occurred every 3 m for 2 yrs, semi-annually for yr 3 and annually for yrs 4 and 5. Relevant for this endpoint was disease status at 3 y.)
- Objective Response Rate by MSKCC Risk Group(Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).)
- Objective Response Rate by UCLA SANI Score(Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).)
- Objective Response Rate by Tumor Type(Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).)
- Objective Response Rate by CA-9 Score (CAIX Classification)(Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).)
- Objective Response Rate by Clear Cell Histology Risk Group(Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Response status was confirmed by an independent assessment of radiographs. Participants received up to 3 courses of 12 weeks duration each.)
- Objective Response Rate by PD-L1 Tumor(Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).)
- Objective Response Rate by B7-H3 Tumor(Disease was evaluated radiologically at baseline and during weeks 8 and 12 of each course. Participants received up to 3 courses of 12 weeks duration each. Median (range) days on treatment: 20 (1-262).)
研究者
David McDermott
Principal Investigator
Beth Israel Deaconess Medical Center