A Randomized Phase II Study of BAY 43-9006 in Combination With Gemcitabine in Metastatic Pancreatic Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Objective Response (OR = CR or PR) as Determined by the RECIST Criteria
研究概览
简要总结
This randomized phase II is studying how well giving sorafenib with or without gemcitabine works in treating patients with metastatic pancreatic cancer. 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. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with gemcitabine may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the objective response rate in patients with metastatic pancreatic cancer treated with concurrent gemcitabine and BAY43-9006 and sequential BAY 43-9006 followed by gemcitabine/BAY 43-9006 at progression.
SECONDARY OBJECTIVES:
I. To determine the six month overall survival rate, 3 month progression free survival rate, time to tumor progression and overall survival of patients with metastatic pancreatic cancer treated with concurrent gemcitabine and BAY43-9006 and sequential BAY 43-9006 followed by gemcitabine/BAY 43-9006 at progression.
II. To determine the safety profile of gemcitabine and BAY43-9006 in patients with metastatic pancreatic cancer and compared to those treated with single agent BAY 43-9006.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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 must have histologically or cytologically confirmed metastatic pancreatic carcinoma
- •Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
- •No prior chemotherapy for metastatic disease is allowed; prior adjuvant chemotherapy is allowed provided that patients did not receive gemcitabine and the chemotherapy completed > 6 months prior to initiation of study therapy
- •Available tumor biopsy specimen (paraffin embedded or fresh frozen) that was obtained at the time of diagnosis and/or prior to study entry is required
- •Life expectancy of greater than 3 months
- •ECOG performance status =< 1
- •Leukocytes >= 3,000/μL
- •Absolute neutrophil count >= 1,500/μL
- •Platelets >= 100,000/μL
- •Hemoglobin >= 9 mg/dL
- •Total bilirubin =< 1.5 X institutional upper limit of normal
- •AST(SGOT)/ALT(SGPT) =< 3 X institutional upper limit of normal, unless the liver is involved with tumor, in which the AST (SGOT)/ALT (SGPT) must be =< 5 X institutional upper limit of normal
- •Creatinine =< 1.5 X institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2
- •The effects of BAY 43-9006 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because raf kinase inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Because BAY 43-9006 is at least partially metabolized by the CYP 3A enzyme in the liver, the possible effect that inhibitors of CYP 3A may have on BAY 43-9006 is unknown; therefore, patients taking inhibitors of CYP 3A (such as ketoconazole, itraconazole, and ritonavir) may not be enrolled in this study
- •Patients may not be receiving any other investigational agents
- •Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to BAY 43-9006 or gemcitabine
- •Secondary primary malignancy (except in situ carcinoma of the cervix, in situ cancer of the prostate, in situ cancer of the breast or adequately treated nonmelanomatous carcinoma of the skin or other malignancy treated at least 5 years previously with no evidence of recurrence); concurrent or history of another malignancy =< 5 years
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant women are excluded from this study because BAY 43-9006 is a kinase inhibitor agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BAY 43-9006, breastfeeding should be discontinued if the mother is treated with BAY 43-9006
- •Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with BAY 43-9006; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
- •Patients with evidence of bleeding diathesis
- •Patients receiving therapeutic doses of anticoagulation; prophylactic anticoagulation (i.e. low dose warfarin) of venous or arterial access devices is allowed
研究组 & 干预措施
Arm I (sorafenib tosylate)
Patients receive 400 mg oral sorafenib twice daily on days 1-28. Patients experiencing disease progression cross over to Arm II.
干预措施: sorafenib tosylate (Drug)
Arm I (sorafenib tosylate)
Patients receive 400 mg oral sorafenib twice daily on days 1-28. Patients experiencing disease progression cross over to Arm II.
干预措施: laboratory biomarker analysis (Other)
Arm II (sorafenib tosylate, gemcitabine hydrochloride)
Patients receive 400 mg oral sorafenib as in Arm I and 1000 mg/m2 gemcitabine IV over 100 minutes on days 1, 8, and 15.
干预措施: sorafenib tosylate (Drug)
Arm II (sorafenib tosylate, gemcitabine hydrochloride)
Patients receive 400 mg oral sorafenib as in Arm I and 1000 mg/m2 gemcitabine IV over 100 minutes on days 1, 8, and 15.
干预措施: gemcitabine hydrochloride (Drug)
Arm II (sorafenib tosylate, gemcitabine hydrochloride)
Patients receive 400 mg oral sorafenib as in Arm I and 1000 mg/m2 gemcitabine IV over 100 minutes on days 1, 8, and 15.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Objective Response (OR = CR or PR) as Determined by the RECIST Criteria
时间窗: Every 6 weeks.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan, MRI, X-ray: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
次要结局
- Overall Survival(From first day of treatment to time of death due to any cause, assessed up to 6 months)
- Progression-free Survival(From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 3 months)