A Pilot Study of Denileukin Diftitox in Combination With High-Dose IL-2 for Patients With Metastatic Renal Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- The primary objective is to assess for toxicity
研究概览
简要总结
RATIONALE: Combinations of biological substances in denileukin diftitox may be able to carry tumor-killing substances directly to kidney cancer cells. Interleukin-2 may stimulate the white blood cells to kill kidney cancer cells. Giving denileukin diftitox together with interleukin-2 may kill more tumor cells.
PURPOSE: This randomized phase I trial is studying the side effects of denileukin diftitox and interleukin-2 in treating patients with metastatic kidney cancer.
详细描述
OBJECTIVES:
Primary
- Determine the toxic effects of denileukin diftitox and high-dose interleukin-2 in patients with metastatic renal cell cancer.
Secondary
- Perform transforming growth factor (TGF)-beta promoter and TGF-beta receptor genotyping to search for variants that may be associated with tumor response to therapy.
- Determine the overall response rate (partial and complete) in patients treated with this regimen.
- Determine the time to progression in patients treated with this regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •DISEASE CHARACTERISTICS:
- •Documented histologically confirmed metastatic renal cell carcinoma
- •Clear cell histology
- •Disease must be measurable as defined by lesions that can be accurately measured in at least one dimension with longest diameter > 20 mm using conventional techniques or > 10 mm with spiral CT scan
- •Must have at least one measurable lesion
- •If the measurable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology
- •Clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules and palpable lymph nodes)
- •The following are considered nonmeasurable lesions:
- •Bone lesions
- •Leptomeningeal disease
- •Pleural/pericardial effusion
- •Inflammatory breast disease
- •Lymphangitis cutis/pulmonis
- •Cystic lesions
- •Abdominal masses not confirmed and followed by imaging techniques
- •No CNS metastases
- •PATIENT CHARACTERISTICS:
- •ECOG performance status < 2
- •Life expectancy of at least 4 months
- •Serum creatinine < 2.0 mg/dL OR creatinine clearance > 50 mL/min
- •Total bilirubin normal
- •Platelets > 100,000/mm³
- •WBC > 3,500/mm³
- •No evidence of congestive heart failure
- •No symptoms of coronary artery disease
- •No serious cardiac arrhythmias
- •A pretreatment cardiac stress test must be performed within 42 days of IL-2 treatment if any cardiac symptoms are present (patients with documented ischemia on the pretreatment cardiac stress test will be excluded from the study)
- •Adequate pulmonary reserve
- •Pulmonary function tests (PFTs) must be performed within 42 days of IL-2 treatment
- •FEV_1 > 2.0 liters of > 75% predicted for height and age
- •Patients unable to perform PFTs will be excluded
- •Women who are pregnant or lactating are not eligible
- •Women of childbearing potential and sexually active males must commit to the use of effective contraception while on study
- •Negative pregnancy test
- •No known HIV-positive patients
- •No evidence of active infection requiring antibiotic therapy
- •Must not have a contraindication to treatment with pressor agents
- •Must not have any significant medical disease that, in the opinion of the investigator, may interfere with completion of the study
- •No history of another malignancy within the past 5 years other than basal cell skin cancer
- •PRIOR CONCURRENT THERAPY:
- •Recovered from all toxic effects of prior therapy
- •Must not currently receive chronic medication for asthma
- •No prior interleukin-2 (IL-2) therapy
- •No prior organ allografts
- •No systemic corticosteroids in the 4 weeks prior to treatment
- •No concurrent systemic steroids
- •No radiotherapy, chemotherapy, or immunotherapy in the 4 weeks prior to the first dose of study treatment
- •No concurrent radiotherapy, chemotherapy, or other immunotherapy
- •No previous investigational agent within 4 weeks prior to the start of study treatment
排除标准
- 未提供
研究组 & 干预措施
C
9 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course
干预措施: aldesleukin (Biological)
C
9 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course
干预措施: denileukin diftitox (Biological)
B
9 mcg/kg Denileukin Diftitox administered IV/daily on days -4 to -2 of standard interleukin 2 dose course
干预措施: denileukin diftitox (Biological)
B
9 mcg/kg Denileukin Diftitox administered IV/daily on days -4 to -2 of standard interleukin 2 dose course
干预措施: aldesleukin (Biological)
A
6 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course
干预措施: denileukin diftitox (Biological)
A
6 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course
干预措施: aldesleukin (Biological)
结局指标
主要结局
The primary objective is to assess for toxicity
时间窗: After each cycle of therapy and 30 days after the last treatment.
To assess the toxicity
次要结局
- The secondary objectives are to investigate differences in peak and duration of the expansion of CD4+, CD8+, CD4+CD 25+ and CD56+(dim and bright)CD25+ cells(Follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 8 weeks.)
- To investigate the effects of denileukin diftitox in combination with IL-2 on plasma TGF-beta levels(Cohort 1: Denileukin diftitox dose of 6μg/kg/ Days 1, 2, 3, 4, and 5. Cohort 2 Denileukin diftitox dose of 9μg/kg given 4, 3, 2, and 1 days prior to 1st day of each cycle. Cohort 3: Denileukin diftitox dose of 9μg/kg given days 8 and 9.)
- To perform TGF-beta promoter and TGF-beta receptor genotyping prior to the start of treatment to search for variants that may be associated with tumor response to therapy.(Cohort 1: Plasma TGF-beta levels to be given on day. Cohort 2: plasma TGF-beta levels to be given at day 1. Cohort 3: plasma TGF-beta levels given on days 1 through 5.)
- Overall response rate and time to progression(CT scans and other pertinent studies will be performed at week 10 to assess response.)
研究者
Timothy Kuzel
Timothy Kuzel, MD
Northwestern University