A Phase I Study Of Peginterferon Alfa-2b (PEG-INTRON) With Sorafenib (Nexavar) In Patients With Unresectable Or Metastatic Clear Cell Renal Carcinoma (RCC).
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose of PEG-interferon Alfa-2b and Sorafenib Tosylate
研究概览
简要总结
RATIONALE: PEG-interferon alfa-2b may interfere with the growth of tumor cells. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also stop the growth of kidney cancer by blocking blood flow to the tumor. Giving PEG-interferon alfa-2b together with sorafenib may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of PEG-interferon alfa-2b and sorafenib in treating patients with unresectable or metastatic kidney cancer.
详细描述
OBJECTIVES:
Primary
- To determine the maximum tolerated dose and toxicity of PEG-interferon alfa-2b and sorafenib tosylate in patients with unresectable or metastatic clear cell renal cell carcinoma.
Secondary
- To determine the progression-free survival of patients treated with this regimen.
- To evaluate, in a preliminary manner, the response rate and overall survival of patients treated with this regimen.
- To evaluate the activation of interferon-induced transcription factors in immune cell subsets (including regulatory T cells [T regs]) using a novel flow cytometric assay and correlate this information with clinical outcome.
- To measure circulating levels of IFN-γ and IL-5 for determination of Th1/Th2 status and CD4+, CD25+, and FoxP3 cell number (T regs) in peripheral blood.
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
- •Must have histologically or cytologically confirmed clear cell renal cell carcinoma (RCC)
- •Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension and is ≥ 1.0 cm by spiral CT scan
- •No prior treatment except
- •PATIENT CHARACTERISTICS:
- •ECOG performance status 0-1
- •Life expectancy > 6 months
- •Good/intermediate Motzer prognostic status
- •ANC ≥ 1,000/mm³
- •Platelet count ≥ 100,000/mm³
- •Hemoglobin ≥ 10.0 g/dL
- •Total bilirubin ≤ 2.0 mg/dL
- •AST and ALT < 2.5 times normal
- •Creatinine ≤ 1.8 mg/dL OR creatinine clearance > 50 mL/min
- •Calcium < 12 mg/dL (when corrected for serum albumin)
- •INR < 1.5 times upper limit of normal
- •Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40% by 2D echo
- •Pulse oximetry ≥ 90% at rest on room air
- •Not pregnant
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No evidence of bleeding diathesis
- •No uncontrolled coagulation disorders
- •No active infections requiring IV antibiotics
- •No known HIV, hepatitis C, or hepatitis B
- •No autoimmune disease requiring ongoing therapy
- •No requirement for adrenal replacement
- •No angina (controlled or uncontrolled)
- •No uncontrolled hypertension
- •No history of other major medical illnesses including, but not limited to, any of the following:
- •Cardiac ischemia
- •Myocardial infarction
- •Major cardiac arrhythmias
- •Inflammatory bowel disorders
- •No other prior malignancy except for previously treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 3 years
- •No significant psychiatric disease that, in the opinion of the principal investigator, would preclude giving adequate informed consent or render immunotherapy unsafe
- •PRIOR CONCURRENT THERAPY:
- •No prior treatment for RCC except sunitinib malate
- •Patients may have progressed or have been intolerant to sunitinib malate
- •No prior systemic treatment for metastatic disease (other than sunitinib malate)
- •No prior organ allografts
- •At least 2 weeks since prior laparoscopic/robotic surgery
- •At least 4 weeks since prior open nephrectomy
- •More than 4 weeks since prior and no concurrent radiotherapy or other surgery
- •More than 4 weeks since prior systemic steroids
- •More than 2 weeks since prior topical, injected, or inhaled steroids
- •No concurrent steroid therapy
- •No concurrent Hypericum perforatum (St. John's wort)
排除标准
- 未提供
研究组 & 干预措施
Peginterferon alfa-2b
Peginterferon alfa-2b will be administered SC on day 1 of each week of therapy. This will most likely be a Monday or a Tuesday. Sorafenib will be initiated on day 15 (start of week 3) of the first course and continued daily without breaks.
干预措施: flow cytometry (Other)
Peginterferon alfa-2b
Peginterferon alfa-2b will be administered SC on day 1 of each week of therapy. This will most likely be a Monday or a Tuesday. Sorafenib will be initiated on day 15 (start of week 3) of the first course and continued daily without breaks.
干预措施: PEG-interferon alfa-2b (Biological)
Peginterferon alfa-2b
Peginterferon alfa-2b will be administered SC on day 1 of each week of therapy. This will most likely be a Monday or a Tuesday. Sorafenib will be initiated on day 15 (start of week 3) of the first course and continued daily without breaks.
干预措施: Sorafenib (Drug)
Peginterferon alfa-2b
Peginterferon alfa-2b will be administered SC on day 1 of each week of therapy. This will most likely be a Monday or a Tuesday. Sorafenib will be initiated on day 15 (start of week 3) of the first course and continued daily without breaks.
干预措施: gene expression analysis (Genetic)
Peginterferon alfa-2b
Peginterferon alfa-2b will be administered SC on day 1 of each week of therapy. This will most likely be a Monday or a Tuesday. Sorafenib will be initiated on day 15 (start of week 3) of the first course and continued daily without breaks.
干预措施: polymerase chain reaction (Genetic)
Peginterferon alfa-2b
Peginterferon alfa-2b will be administered SC on day 1 of each week of therapy. This will most likely be a Monday or a Tuesday. Sorafenib will be initiated on day 15 (start of week 3) of the first course and continued daily without breaks.
干预措施: reverse transcriptase-polymerase chain reaction (Genetic)
Peginterferon alfa-2b
Peginterferon alfa-2b will be administered SC on day 1 of each week of therapy. This will most likely be a Monday or a Tuesday. Sorafenib will be initiated on day 15 (start of week 3) of the first course and continued daily without breaks.
干预措施: immunoenzyme technique (Other)
Peginterferon alfa-2b
Peginterferon alfa-2b will be administered SC on day 1 of each week of therapy. This will most likely be a Monday or a Tuesday. Sorafenib will be initiated on day 15 (start of week 3) of the first course and continued daily without breaks.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Maximum Tolerated Dose of PEG-interferon Alfa-2b and Sorafenib Tosylate
时间窗: up to 2 months
Characterize the Toxicity of Peginterferon Alfa-2b and Sorafenib in Patients With Metastatic or Unresectable Clear Cell Renal Cell Carcinoma.
时间窗: up to 2 months
次要结局
- Progression-free Survival of Patients Receiving Peginterferon Alfa-2b and Sorafenib.(up to 1 year)
- Response Rate of Patients Receiving Peginterferon Alfa-2b and Sorafenib.(up to 1 year)
- Overall Survival(up to 1 year)
- Activation of Interferon-induced Transcription Factors in Immune Cell Subsets by Flow Cytometry and Correlation of This Information With Clinical Outcome(up to 1 year)
- Circulating Levels of IFN-γ and IL-5 for Determination of Th1/Th2 Status and CD4+, CD25+, and FoxP3 Cell Number (T Regs) in Peripheral Blood(Up to 1 year)
研究者
Thomas Olencki
Principal Investigator
Ohio State University Comprehensive Cancer Center