Randomized Study of Sorafenib Dose Escalation in Patients With Previously Untreated Metastatic Renal Cell Carcinoma
Randomized Phase IIb Study of Sorafenib Dose Escalation in Patients With Previously Untreated Metastatic Renal Cell Carcinoma (RCC)
The primary objective of this study is to compare the effectiveness of a dose-escalation regimen (400 to 800mg bid) relative to the standard dosing regimen (400mg bid) of sorafenib given in patients with metastatic RCC.
The secondary objectives are to evaluate the effects of the dose-escalation regimen on the quality of life (QoL) of patients with metastatic RCC and to characterize the safety and tolerability profile of a dose-escalation regimen of sorafenib in patients with metastatic RCC.
研究概览
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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Arkansas
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Jonesboro、Arkansas、美国、72401
- Clopton Clinic
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California
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La Verne、California、美国、91750
- Wilshire Oncology Medical Group, Inc.
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Florida
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Miami、Florida、美国、33176
- Advanced Medical Specialties
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Georgia
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Athens、Georgia、美国、30607
- Northeast Georgia Cancer Care
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Atlanta、Georgia、美国、30309
- Peachtree Hematology Oncology Consultants
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Macon、Georgia、美国、31201
- Central Georgia Cancer Care
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Marietta、Georgia、美国、30060
- Northwest Georgia Oncology Centers
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Illinois
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Normal、Illinois、美国、61761
- Mid-Illinois Hematology and Oncology Associates, Ltd.
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Montana
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Billings、Montana、美国、59101
- Hematology Oncology Centers of the Northern Rockies
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North Carolina
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Gastonia、North Carolina、美国、28054
- Gaston Hematology and Oncology
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Oregon
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Beaverton、Oregon、美国、97006
- Pacific Oncology, PC
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Pennsylvania
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Lancaster、Pennsylvania、美国、17605
- The Lancaster Cancer Center, Ltd
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Tennessee
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Memphis、Tennessee、美国、38120
- The West Clinic
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Age ≥18 years old.
- Diagnosis of unresectable/metastatic renal cell carcinoma (RCC). Nonclear cell histology is permitted (except for medullary, collecting duct, or sarcomatoid >50% of specimen). Prior metastasectomy is permitted as long as there is measurable disease at time of consent.
- Karnofsky Performance Status of 50% or greater at study entry.
- Adequate bone marrow, liver and renal function as assessed by the following: o Hemoglobin ≥ 9.0 g/dL. o ANC ≥ 1500/mm3. o Platelet count ≥ 100,000/mm3. o Total bilirubin ≤ 1.5 ULN. o ALT and AST ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver involvement). o Creatinine ≤ 1.5 × ULN.
- Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to the start of treatment.
- Women of childbearing potential and sexually active men must agree to use adequate barrier contraception prior to study entry, for the duration of study participation, and for at least three months after the last administration of sorafenib.
- INR < 1.5 or a PT/ PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
- Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
Exclusion Criteria:
- Prior systemic anticancer treatment for metastatic disease, including investigational therapy.
- Prior treatment with bevacizumab, sunitinib, or sorafenib even in the adjuvant setting.
- Prior cytokine therapy with interleukin (IL)-2 or interferon (IFN) for metastatic disease.
- Active malignancy other than RCC (except non-melanoma skin cancer) within 5 years of enrollment.
- Hemodialysis or peritoneal dialysis.
- Treatment with radiotherapy within 2 weeks of enrollment.
- Cardiac disease: Congestive heart failure Class II or higher per NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
- Uncontrolled CNS metastases. All patients must undergo a CT) scan/MRI of the brain to exclude brain metastasis. Patients with adequately treated CNS disease may be considered for participation as long as the first dose of sorafenib is 4 weeks after completion of CNS therapy.
- Uncontrolled hypertension defined as SBP > 150 mmHg or DBP > 90 mmHg, despite optimal medical management.
- Active clinically serious infection > Grade 2 per the CTCAE v3.
- Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
- Pulmonary hemorrhage/bleeding event ≥ Grade 2 per CTCAE v3.0 within 4 weeks of administration of the first dose of study drug.
- Any other hemorrhage/bleeding event ≥ Grade 3 per CTCAE v3.0 within 4 weeks of administration of the first dose of study drug.
- Serious non-healing wound, ulcer, or bone fracture.
- Evidence or history of bleeding diathesis or coagulopathy.
- Major surgery, open biopsy or significant traumatic injury within 4 weeks of administration of the first study drug dose.
- Use of St. John's Wort, rifampin (rifampicin), phenytoin, Phenobarbital, carbamazepine, dexamethasone.
- Known or suspected allergy to sorafenib or any agent given in the course of this trial.
- Any condition that impairs patient's ability to swallow whole pills.
- Any malabsorption problem.
- Pregnancy or lactation.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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有源比较器:Group A: Escalated Dose
Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen).
Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2).
Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12.
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Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2).
Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12.
其他名称:
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有源比较器:Group B: Standard Dose
Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen).
Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study.
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Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study.
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.
大体时间:Overall response will be measured at baseline and every 8 weeks , unless clinically indicated prior to that, until the end of treatment.
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Response was evaluated via changes from baseline in radiological tumor measurements performed every 8 weeks and at the end of treatment unless clinically indicated prior to that.
Confirmatory scans were to be obtained no less than 4 weeks but no more than 6 weeks following initial documentation of objective response.
Response was evaluated using RECIST criteria, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease; Progressive disease (PD) is at least a 20% increase in the sum of LD of target lesions or the appearance of one or more new lesions.
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Overall response will be measured at baseline and every 8 weeks , unless clinically indicated prior to that, until the end of treatment.
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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PFS Rate at 9, 13 and 17 Months
大体时间:PFS was to be measured at 9, 13, and 17 months.
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Due to the early study closure and the small sample size, the PFS rate at 9, 13, and 17 months were not evaluated.
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PFS was to be measured at 9, 13, and 17 months.
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Overall Survival Rate
大体时间:Overall survival was measured from day 1 of treatment until the end of treatment and then every 4 months thereafter until death.
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Due to the early study closure and the small sample size, overall survival rate was not evaluated.
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Overall survival was measured from day 1 of treatment until the end of treatment and then every 4 months thereafter until death.
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Changes From Baseline in Symptom Burden
大体时间:The PCM was administered during screening, at each scheduled visit (approximately every 4 weeks), and at the end of treatment visit.
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The Patient Care Monitor Version 2.0 (PCM) is an tablet computer based assessment system that measures patient reported outcomes (PROs) in medical patients with a particular emphasis on symptoms related to cancer and its treatment. The PCM comprises 86 items which include 8 items answered only by females (e.g. menstrual cramping). Each item is presented so that the patient rates the degree to which the item has been a problem in the past week (0 not a problem to 10 as bad as possible). |
The PCM was administered during screening, at each scheduled visit (approximately every 4 weeks), and at the end of treatment visit.
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合作者和调查者
合作者
调查人员
- 首席研究员:Vasily Assikis, MD、Acorn Cardiovascular, Inc.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
Sorafenib Escalated Dose的临床试验
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University of South CarolinaMedical University of South Carolina; National Institute on Deafness and Other Communication...完全的
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Jiangsu Province Centers for Disease Control and...Academy of Military Medical Sciences,Academy of Military Sciences,PLA; ZHONGYIANKE Biotech Co... 和其他合作者招聘中