A Phase II Neoadjuvant Clinical Trial to Evaluate the Efficacy of BAY 43-9006 (Sorafenib) in Metastatic Renal Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Efficacy of BAY 43-9006 by Evaluating Response Rate
研究概览
简要总结
Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sorafenib before and after surgery may be an effective treatment for kidney cancer. This phase II trial is studying how well sorafenib works in treating patients who are undergoing surgery for metastatic kidney cancer.
详细描述
PRIMARY OBJECTIVES:
I. Efficacy of BAY 43-9006 (sorafenib tosylate) by evaluating response rate. II. Toxicities of BAY 43-9006 in metastatic renal cell carcinoma (RCC). III. Intraoperative and peri/postoperative safety of BAY 43-9006.
SECONDARY OBJECTIVES:
I. Time to progression. II. Duration of response. II. Overall Survival.
TERTIARY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Patients with histologically or cytologically confirmed metastatic clear cell RCC who are eligible for cytoreductive nephrectomy as agreed upon by Medical Oncology and Urology team members; patients with metastatic disease eligible for cytoreductive nephrectomy should have the following characteristics: resectable primary tumor (no gross adjacent organ invasion, no or minimal abdominal lymphadenopathy, no or minimal inferior vena caval involvement), bulk of metastatic disease within the primary tumor, absence of multiple liver metastases, no more than 2 organ sites involved with metastases
- •Patients must have measurable disease, defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures >= 20 mm with conventional techniques or >= 10 mm with spiral computed tomography (CT) scan
- •ECOG performance status =< 1
- •Absolute neutrophil count >= 1,500/uL
- •Platelets >= 100,000/uL
- •Hgb > 9.0 g/dL
- •Total bilirubin =< 2.0 mg/dl
- •Albumin > 3.0 g/dL
- •Serum creatinine =< 2.0 mg/dl
- •AST (SGOT) and/or ALT (SGPT) =< 2.5 x institutional upper limit of normal for subjects without evidence of liver metastases
- •AST (SGOT) and/or ALT (SGPT) =< 5 X institutional upper limit of normal for subjects with documented liver metastases
- •Female patients of childbearing potential must have a normal plasma beta human chorionic gonadotropin (beta-HCG) within 24 hours prior to enrolling in the study due to the possible teratogenic effect; however, patients will be eligible if their beta-HCG is elevated and is determined to be due to malignancy
- •Patients of child fathering or childbearing potential must agree to practice a form of medically acceptable birth control while on study
- •Patients must give written informed consent prior to initiation of therapy, in keeping with the policies of the institution; patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy
- •Patients must have ability to comply with study and/or follow-up procedures
- •Prior biopsy material (blocks or unstained slides) must be available for comparison purposes
排除标准
- •No prior malignancy is allowed, except for non-melanoma skin cancer, in situ carcinoma of any site, or other cancers for which the patient has been adequately treated and disease free for 5 years
- •Patients must not have received any systemic anticancer therapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Patients must not be scheduled to receive another experimental drug while on this study; patients are permitted to be on concomitant bisphosphonates
- •Patients who are incapable of swallowing pills are excluded from this study
- •Patients must not have a primary brain tumor, any brain metastases, leptomeningeal disease, seizure disorders not controlled with standard medical therapy, or history of stroke
- •Patients must not have active acute infections that could be worsened by anticancer therapy or interfere with this study
- •Patients must not have clinically significant cardiovascular disease, recent myocardial infarction (i.e. last 6 months), (unstable angina), New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac dysrhythmia requiring medication, or peripheral vascular disease (grade II or greater)
- •Patients must not have history of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications
- •Patients with uncontrolled hypertension > 140/90 are excluded from the study
- •Patients must not have any history of bleeding diathesis; patients must not be on therapeutic anticoagulation; prophylactic anticoagulation (i.e. low dose coumadin) of venous or arterial access devices is allowed provided that the requirements for PT, INR or PTT are met
- •Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with BAY 43-9006
- •HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study
研究组 & 干预措施
Group I (cytoreductive nephrectomy and sorafenib tosylate)
Patients undergo cytoreductive nephrectomy on day 1. Patients then receive oral sorafenib twice daily on days 15-84.
In all groups, patients with stable or regressing disease continue to receive oral sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Some patients may continue treatment for longer than 1 year at the discretion of the investigator.
干预措施: therapeutic conventional surgery (Procedure)
Group I (cytoreductive nephrectomy and sorafenib tosylate)
Patients undergo cytoreductive nephrectomy on day 1. Patients then receive oral sorafenib twice daily on days 15-84.
In all groups, patients with stable or regressing disease continue to receive oral sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Some patients may continue treatment for longer than 1 year at the discretion of the investigator.
干预措施: sorafenib tosylate (Drug)
Group I (cytoreductive nephrectomy and sorafenib tosylate)
Patients undergo cytoreductive nephrectomy on day 1. Patients then receive oral sorafenib twice daily on days 15-84.
In all groups, patients with stable or regressing disease continue to receive oral sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Some patients may continue treatment for longer than 1 year at the discretion of the investigator.
干预措施: laboratory biomarker analysis (Other)
Group II (sorafenib tosylate and cytoreductive nephrectomy)
Patients receive oral sorafenib twice daily on days 1-7. Patients undergo cytoreductive nephrectomy on day 8. Patients then receive oral sorafenib twice daily on days 22-84.
In all groups, patients with stable or regressing disease continue to receive oral sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Some patients may continue treatment for longer than 1 year at the discretion of the investigator.
干预措施: therapeutic conventional surgery (Procedure)
Group II (sorafenib tosylate and cytoreductive nephrectomy)
Patients receive oral sorafenib twice daily on days 1-7. Patients undergo cytoreductive nephrectomy on day 8. Patients then receive oral sorafenib twice daily on days 22-84.
In all groups, patients with stable or regressing disease continue to receive oral sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Some patients may continue treatment for longer than 1 year at the discretion of the investigator.
干预措施: sorafenib tosylate (Drug)
Group II (sorafenib tosylate and cytoreductive nephrectomy)
Patients receive oral sorafenib twice daily on days 1-7. Patients undergo cytoreductive nephrectomy on day 8. Patients then receive oral sorafenib twice daily on days 22-84.
In all groups, patients with stable or regressing disease continue to receive oral sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Some patients may continue treatment for longer than 1 year at the discretion of the investigator.
干预措施: laboratory biomarker analysis (Other)
Group III (sorafenib tosylate and cytoreductive nephrectomy)
Patients receive oral sorafenib twice daily on days 1-28. Patients undergo cytoreductive nephrectomy on day 29. Patients then receive oral sorafenib twice daily on days 43-84.
In all groups, patients with stable or regressing disease continue to receive oral sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Some patients may continue treatment for longer than 1 year at the discretion of the investigator.
干预措施: therapeutic conventional surgery (Procedure)
Group III (sorafenib tosylate and cytoreductive nephrectomy)
Patients receive oral sorafenib twice daily on days 1-28. Patients undergo cytoreductive nephrectomy on day 29. Patients then receive oral sorafenib twice daily on days 43-84.
In all groups, patients with stable or regressing disease continue to receive oral sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Some patients may continue treatment for longer than 1 year at the discretion of the investigator.
干预措施: sorafenib tosylate (Drug)
Group III (sorafenib tosylate and cytoreductive nephrectomy)
Patients receive oral sorafenib twice daily on days 1-28. Patients undergo cytoreductive nephrectomy on day 29. Patients then receive oral sorafenib twice daily on days 43-84.
In all groups, patients with stable or regressing disease continue to receive oral sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Some patients may continue treatment for longer than 1 year at the discretion of the investigator.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Efficacy of BAY 43-9006 by Evaluating Response Rate
时间窗: Every 2 weeks during 4 week cycle
Response rate (participants with response/total number participants) where number of participants with response evaluated using international criteria proposed by (RECIST) Committee of: Complete Response: Disappearance all target lesions; Partial Response (PR): \> 30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD. Progressive Disease (PD): \> 20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of 1 or \> new lesions; Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum LD since treatment started.
次要结局
未报告次要终点