A Phase II Clinical and Correlative Study of BAY 43-9006 (Sorafenib) IND 69,896 in Sarcoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Change in Fludeoxyglucose (FDG) Uptake (Maximal Standardized Uptake Value, or SUVmax)
研究概览
简要总结
This phase II trial is studying how well sorafenib works in treating patients with soft tissue sarcoma. Sorafenib may stop the growth of soft tissue sarcoma by blocking blood flow to the tumor and blocking some of the enzymes needed for tumor cell growth
详细描述
PRIMARY OBJECTIVES:
I. To determine if the combined vascular endothelial growth factor receptor 2 (VEGF-R2)/platelet-derived growth factor receptor (PDGFR)-beta inhibitor BAY 43-9006/ sorafenib can decrease interstitial fluid pressure (IFP) in soft tissue sarcomas.
II. To investigate the effects of BAY 43-9006/sorafenib on tumor blood flow, circulating endothelial cells, vascular density and pericyte coverage.
III. To characterize the pharmacokinetics of BAY 43-9006/sorafenib in sarcoma patients.
SECONDARY 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
- •There are two groups of patients eligible for this study; treatment group 1 consists of patients with extremity sarcomas other than potentially curable osteosarcoma or Ewing's sarcoma who are candidates for potentially curative surgery; treatment group 2 consists of patients with metastatic or inoperable sarcoma, for which there is no known curative or survival prolonging palliative therapy, or failure of these therapies; patients must have at least one site of measurable disease by radiologic imaging techniques; patients must have at least one palpable tumor mass with no overlying viscera which is amenable to biopsy; the tumor mass should be approximately 2 cm or greater in diameter; patients with smaller palpable tumors are eligible if participation is approved by the treating surgeon after discussion with the study chairperson
- •As of 5/30/07, no subjects will accrue to Treatment Group I
- •Life expectancy >= 2 months
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Pretreatment laboratory data, obtained within 14 days of study entry, must meet the following criteria:
- •Absolute Neutrophil Count (ANC) >= 1,500/mm^3
- •Platelets >= 100,000/mm^3
- •Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5-times the upper limit of normal (ULN)
- •Serum glutamic-pyruvic transaminase (SGPT)=< 2.5-times ULN
- •Total Bilirubin =< ULN
- •Serum creatinine =< 1.5-times ULN
- •>= 3 weeks since major surgery unrelated to study disease (sarcoma)
- •>= 3 weeks since chemotherapy or radiation therapy (6 weeks for nitrosourea or mitomycin C chemotherapy)
- •No prior treatment with sorafenib (BAY 43-9006) or specific inhibitors of mitogen-activated protein kinase (MAPK) pathways are permitted; a previously irradiated tumor site cannot be used for clinical or correlative measurements, although irradiation to sites other than a measurable site is permitted; there are no limitations on the extent or type of prior therapy received by the patient other than the time intervals indicated in the above and demonstrating complete recovery from any adverse effects associated by satisfying all relevant eligibility criteria
- •Patients who are on warfarin anticoagulation are allowed to participate as long as they are converted to a low molecular weight heparin (e.g. lovenox) from study entry until at least day 56
- •Women of childbearing potential must not be pregnant or lactating; all women of childbearing potential (age < 50, last menstrual period [LMP] < 12 months ago) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L of beta-HCG) within 72 hr prior to receiving the study medication; BAY43-9006 has antiproliferative effects, which may be harmful to the developing fetus or nursing infant
- •Fertile males and females must use adequate contraception
- •Signed informed consent
排除标准
- •Ewing's sarcoma or osteosarcoma that is potentially curable with surgery, chemotherapy, and/or radiation therapy
- •Active brain metastases including evidence of cerebral edema by CT scan or MRI, or progression from prior imaging study, any requirements for steroids, or enzyme-inducing anti-convulsant agents, or clinical symptoms of/from brain metastases; patients with treated and/or stable brain metastasis who are asymptomatic can be enrolled, if otherwise eligible
- •Any uncontrolled serious medical or psychiatric illness; particular note is given to uncontrolled hypertension (discretion left to investigators) and significant proteinuria > 1 gm/24 hr (does not require quantitation in absence of clinical indication)
- •Patients receiving other investigational agents
- •Human immunodeficiency virus (HIV) patients receiving combination anti-retroviral therapy are excluded because of potential pharmacokinetic interactions
研究组 & 干预措施
Group I (sarcomas of extremity, closed accrual as of 5/30/07)
Patients receive oral sorafenib twice daily on days 1-14. Patients undergo surgical resection of the tumor on approximately day 15. Once patients recover from surgery (and radiotherapy if indicated), patients who demonstrate a clinically and pathologically significant response (≥ 25% reduction in tumor size or ≥ 25% necrosis in the surgical specimen) may continue sorafenib as above for a maximum of 6 months in the absence of disease progression or unacceptable toxicity and at the discretion of the principal investigator. Biopsy tissue and blood samples are examined for biomarkers and interstitial fluid pressure (IFP) is measured at baseline and immediately before surgery.
干预措施: sorafenib tosylate (Drug)
Group I (sarcomas of extremity, closed accrual as of 5/30/07)
Patients receive oral sorafenib twice daily on days 1-14. Patients undergo surgical resection of the tumor on approximately day 15. Once patients recover from surgery (and radiotherapy if indicated), patients who demonstrate a clinically and pathologically significant response (≥ 25% reduction in tumor size or ≥ 25% necrosis in the surgical specimen) may continue sorafenib as above for a maximum of 6 months in the absence of disease progression or unacceptable toxicity and at the discretion of the principal investigator. Biopsy tissue and blood samples are examined for biomarkers and interstitial fluid pressure (IFP) is measured at baseline and immediately before surgery.
干预措施: therapeutic conventional surgery (Procedure)
Group I (sarcomas of extremity, closed accrual as of 5/30/07)
Patients receive oral sorafenib twice daily on days 1-14. Patients undergo surgical resection of the tumor on approximately day 15. Once patients recover from surgery (and radiotherapy if indicated), patients who demonstrate a clinically and pathologically significant response (≥ 25% reduction in tumor size or ≥ 25% necrosis in the surgical specimen) may continue sorafenib as above for a maximum of 6 months in the absence of disease progression or unacceptable toxicity and at the discretion of the principal investigator. Biopsy tissue and blood samples are examined for biomarkers and interstitial fluid pressure (IFP) is measured at baseline and immediately before surgery.
干预措施: laboratory biomarker analysis (Other)
Group I (sarcomas of extremity, closed accrual as of 5/30/07)
Patients receive oral sorafenib twice daily on days 1-14. Patients undergo surgical resection of the tumor on approximately day 15. Once patients recover from surgery (and radiotherapy if indicated), patients who demonstrate a clinically and pathologically significant response (≥ 25% reduction in tumor size or ≥ 25% necrosis in the surgical specimen) may continue sorafenib as above for a maximum of 6 months in the absence of disease progression or unacceptable toxicity and at the discretion of the principal investigator. Biopsy tissue and blood samples are examined for biomarkers and interstitial fluid pressure (IFP) is measured at baseline and immediately before surgery.
干预措施: pharmacological study (Other)
Group I (sarcomas of extremity, closed accrual as of 5/30/07)
Patients receive oral sorafenib twice daily on days 1-14. Patients undergo surgical resection of the tumor on approximately day 15. Once patients recover from surgery (and radiotherapy if indicated), patients who demonstrate a clinically and pathologically significant response (≥ 25% reduction in tumor size or ≥ 25% necrosis in the surgical specimen) may continue sorafenib as above for a maximum of 6 months in the absence of disease progression or unacceptable toxicity and at the discretion of the principal investigator. Biopsy tissue and blood samples are examined for biomarkers and interstitial fluid pressure (IFP) is measured at baseline and immediately before surgery.
干预措施: computed tomography (Procedure)
Group I (sarcomas of extremity, closed accrual as of 5/30/07)
Patients receive oral sorafenib twice daily on days 1-14. Patients undergo surgical resection of the tumor on approximately day 15. Once patients recover from surgery (and radiotherapy if indicated), patients who demonstrate a clinically and pathologically significant response (≥ 25% reduction in tumor size or ≥ 25% necrosis in the surgical specimen) may continue sorafenib as above for a maximum of 6 months in the absence of disease progression or unacceptable toxicity and at the discretion of the principal investigator. Biopsy tissue and blood samples are examined for biomarkers and interstitial fluid pressure (IFP) is measured at baseline and immediately before surgery.
干预措施: dynamic contrast-enhanced magnetic resonance imaging (Procedure)
Group II (metastatic or inoperable sarcomas)
Patients receive oral sorafenib twice daily on days 1-28. Treatment repeats every 28 days for 2 courses. Patients with responding or stable disease may continue sorafenib in the absence of disease progression or unacceptable toxicity. Biopsy tissue and blood samples are examined for biomarkers and IFP is measured at baseline and on days 28 and 56.
干预措施: sorafenib tosylate (Drug)
Group II (metastatic or inoperable sarcomas)
Patients receive oral sorafenib twice daily on days 1-28. Treatment repeats every 28 days for 2 courses. Patients with responding or stable disease may continue sorafenib in the absence of disease progression or unacceptable toxicity. Biopsy tissue and blood samples are examined for biomarkers and IFP is measured at baseline and on days 28 and 56.
干预措施: laboratory biomarker analysis (Other)
Group II (metastatic or inoperable sarcomas)
Patients receive oral sorafenib twice daily on days 1-28. Treatment repeats every 28 days for 2 courses. Patients with responding or stable disease may continue sorafenib in the absence of disease progression or unacceptable toxicity. Biopsy tissue and blood samples are examined for biomarkers and IFP is measured at baseline and on days 28 and 56.
干预措施: pharmacological study (Other)
Group II (metastatic or inoperable sarcomas)
Patients receive oral sorafenib twice daily on days 1-28. Treatment repeats every 28 days for 2 courses. Patients with responding or stable disease may continue sorafenib in the absence of disease progression or unacceptable toxicity. Biopsy tissue and blood samples are examined for biomarkers and IFP is measured at baseline and on days 28 and 56.
干预措施: computed tomography (Procedure)
Group II (metastatic or inoperable sarcomas)
Patients receive oral sorafenib twice daily on days 1-28. Treatment repeats every 28 days for 2 courses. Patients with responding or stable disease may continue sorafenib in the absence of disease progression or unacceptable toxicity. Biopsy tissue and blood samples are examined for biomarkers and IFP is measured at baseline and on days 28 and 56.
干预措施: dynamic contrast-enhanced magnetic resonance imaging (Procedure)
结局指标
主要结局
Change in Fludeoxyglucose (FDG) Uptake (Maximal Standardized Uptake Value, or SUVmax)
时间窗: Baseline to up to 1 month post-treatment
Paired comparison made using a Wilcoxon signed rank test with one-sided type I error of 5%.
Change in Interstitial Fluid Pressure (IFP)
时间窗: Baseline to up to 1 month post-treatment
Paired comparison made using a Wilcoxon signed rank test with one-sided type I error of 5%.
Change in White Blood Cell Count (WBC)
时间窗: Baseline to up to 1 month post-treatment
Paired comparison made using a Wilcoxon signed rank test with one-sided type I error of 5%.
Change in Pericyte Coverage of Endothelial Cells (Alpha-SMA)
时间窗: Baseline to up to 1 month post-treatment
Paired comparison made using a Wilcoxon signed rank test with one-sided type I error of 5%.
Clinical Benefit as Measured by 50% Reduction in IFP
时间窗: Baseline to surgery
Clinical Benefit, Measured by Any Reduction in Tumor Dimensions on CT Scan as Measured by RECIST Criteria
时间窗: Up to 1 month
Incidence of Adverse Events
时间窗: Up to 1 month
次要结局
未报告次要终点