Sorafenib and Erlotinib in Treating Patients With Metastatic or Unresectable Solid Tumors
A Phase I Study of BAY 43-9006 (Sorafenib) in Combination With OSI-774 (Erlotinib; Tarceva) in Advanced Solid Tumors
RATIONALE: Sorafenib and erlotinib may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of sorafenib and erlotinib in treating patients with metastatic or unresectable solid tumors.
研究概览
详细说明
OBJECTIVES:
Primary
- Determine the maximum tolerated dose and recommended phase II dose of sorafenib and erlotinib in patients with metastatic or unresectable solid tumors.
Secondary
- Determine the optimal biologically effective dose of this regimen that will lead to hypophosphorylation of epidermal growth factor receptor (EGFR), ERK, Akt, and vascular endothelial growth factor receptor (VEGFR), and inhibition of angiogenesis and apoptosis with tolerable toxicity in these patients.
- Correlate the pharmacokinetic profiles of this regimen with toxicity and biological activity in these patients.
- Determine, preliminarily, the antitumor activity of this regimen in these patients.
- Correlate phosphorylation status of EGFR, ERK, Akt, and VEGFR with antitumor activity of this regimen in these patients.
OUTLINE: This is a multicenter, open label, non-randomized, dose-escalation study.
Patients receive oral sorafenib alone once or twice daily on days -6 to 0*. Patients then receive oral sorafenib once or twice daily and oral erlotinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
NOTE: *Not considered part of course 1; considered a "run-in" period only.
Cohorts of 3-6 patients receive escalating doses of sorafenib and erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients are treated at the MTD.
After completion of study treatment, patients are followed at 4 weeks and then at least annually thereafter.
PROJECTED ACCRUAL: A total of 16-28 patients will be accrued for this study within 5-14 months.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
-
-
Ontario
-
Hamilton、Ontario、加拿大、L8V 5C2
- Margaret and Charles Juravinski Cancer Centre
-
Toronto、Ontario、加拿大、M5G 2M9
- Princess Margaret Hospital
-
-
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
DISEASE CHARACTERISTICS:
Histologically confirmed solid tumor
- Metastatic or unresectable disease
- Standard curative or palliative measures do not exist OR are no longer effective
- Measurable disease by radiography (for patients treated at the maximum tolerated dose [MTD] only)
- Tumor accessible for serial biopsies (for patients treated at the MTD only)
- No known brain metastases
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2 OR
- Karnofsky 60-100%
Life expectancy
- More than 12 weeks
Hematopoietic
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- No bleeding diathesis or coagulopathy
Hepatic
- Bilirubin normal
- AST and ALT ≤ 2.5 times ULN
- PT INR ≤ 1.5 unless on full-dose warfarin
Renal
- Creatinine normal OR
- Creatinine clearance ≥ 60 mL/min
Cardiovascular
- No uncontrolled hypertension (i.e., systolic blood pressure [BP] > 140 mm Hg or diastolic BP > 90 mm Hg despite medication)
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
Ophthalmic
No abnormalities of the cornea, including any of the following:
- Dry eye syndrome
- Sjögren's syndrome
- Congenital abnormalities (e.g., Fuch's dystrophy)
- Abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
- Abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)
Gastrointestinal
- No active peptic ulcer disease that would impair the ability to swallow pills
- No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Willing to undergo serial biopsies, positron emission tomography, and CT scanning (for patients treated at the MTD only)
- No ongoing or active infection
- No significant traumatic injury within the past 3 weeks
- No history of allergic reaction to drugs of similar chemical or biological composition to study drugs
- No psychiatric illness or social situation that would preclude study compliance
- No other condition that would impair the ability to swallow pills
- No other uncontrolled illness
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent prophylactic hematopoietic colony-stimulating factors
Chemotherapy
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
Endocrine therapy
- Not specified
Radiotherapy
- More than 4 weeks since prior radiotherapy (except for low dose, non-myelosuppressive radiotherapy) and recovered
Surgery
- More than 3 weeks since prior major surgery
- No prior surgical procedure affecting absorption
Other
- No prior sorafenib or erlotinib
- No other prior agents targeting Raf, vascular endothelial growth factor (VEGF), VEGF receptor, or epidermal growth factor receptor
- No other concurrent investigational agents
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)
- No concurrent CYP3A4 inducers (e.g., rifampin or Hypericum perforatum [St. John's wort])
- No other concurrent anticancer therapy
- Concurrent prophylactic anticoagulation therapy (e.g., low-dose warfarin) allowed provided PT INR < 1.1 times upper limit of normal (ULN)
Concurrent full-dose anticoagulants (e.g., warfarin) with PT INR > 1.5 allowed provided both of the following criteria are met:
- Patient has an in range INR (between 2-3) while on a stable-dose of oral anti-coagulant OR a stable-dose of low molecular weight heparin
- No active bleeding OR pathological condition that would confer a high risk of bleeding (e.g., tumor involving a major vessel or known varices)
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的:OSI-774 erlotinib) and Bay 43-9006 (Sorafenib)
Sorafenib administered alone for a 1-week run-in period, and then both drugs e given together continuously, with every 28 days considered as a cycle.
Three dose levels assessed.
|
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
Maximum tolerated dose and recommended phase II dose
大体时间:28 days
|
28 days
|
次要结果测量
结果测量 |
大体时间 |
---|---|
Pharmacodynamic outcomes
大体时间:Pre study and cycle 1
|
Pre study and cycle 1
|
Pharmacokinetic outcomes
大体时间:Pre-study, cycle 1 and cycle 2
|
Pre-study, cycle 1 and cycle 2
|
Antitumor activity
大体时间:Every 8 wks
|
Every 8 wks
|
Correlation of EGFR, AKT, ERK and VEGFR with antitumor activity
大体时间:If responses or prolonged stable disease are observed
|
If responses or prolonged stable disease are observed
|
EGFR activating mutations, gene amplification status, EGFR intron 1 polymorphism if responses or prolonged disease stabilization are seen
大体时间:If responses or prolonged stable disease are observed
|
If responses or prolonged stable disease are observed
|
合作者和调查者
调查人员
- 学习椅:Lillian L. Siu, MD, FRCPC、Princess Margaret Hospital, Canada
出版物和有用的链接
一般刊物
- Quintela-Fandino M, Le Tourneau C, Duran I, Chen EX, Wang L, Tsao M, Bandarchi-Chamkhaleh B, Pham NA, Do T, MacLean M, Nayyar R, Tusche MW, Metser U, Wright JJ, Mak TW, Siu LL. Phase I combination of sorafenib and erlotinib therapy in solid tumors: safety, pharmacokinetic, and pharmacodynamic evaluation from an expansion cohort. Mol Cancer Ther. 2010 Mar;9(3):751-60. doi: 10.1158/1535-7163.MCT-09-0868. Epub 2010 Mar 2.
- Duran I, Hotte SJ, Hirte H, Chen EX, MacLean M, Turner S, Duan L, Pond GR, Lathia C, Walsh S, Wright JJ, Dancey J, Siu LL. Phase I targeted combination trial of sorafenib and erlotinib in patients with advanced solid tumors. Clin Cancer Res. 2007 Aug 15;13(16):4849-57. doi: 10.1158/1078-0432.CCR-07-0382.
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.
盐酸厄洛替尼的临床试验
-
M.D. Anderson Cancer Center撤销转移性肺非小细胞癌 | IVA 期肺癌 AJCC v8 | IVB 期肺癌 AJCC v8 | IV 期肺癌 AJCC v8
-
Washington University School of MedicineGenentech, Inc.终止
-
Mayo Clinic完全的转移性结直肠腺癌 | 转移性结肠腺癌 | 转移性结直肠癌 | 转移性直肠腺癌 | IV 期结直肠癌 AJCC v8 | IVA 期结直肠癌 AJCC v8 | IVB 期结直肠癌 AJCC v8 | IVC 期结直肠癌 AJCC v8 | 转移性微卫星稳定性结直肠癌 | 转移性微卫星稳定性结肠癌 | 微卫星稳定性直肠癌美国
-
City of Hope Medical CenterNational Cancer Institute (NCI)完全的IV 期结直肠癌 AJCC v7 | IVA 期结直肠癌 AJCC v7 | IVB 期结直肠癌 AJCC v7 | 转移性结直肠癌 | III 期结肠癌 AJCC v7 | III 期直肠癌 AJCC v7 | IIIA 期结肠癌 AJCC v7 | IIIA 期直肠癌 AJCC v7 | IIIB 期结肠癌 AJCC v7 | IIIB 期直肠癌 AJCC v7 | IIIC 期结肠癌 AJCC v7 | IIIC 期直肠癌 AJCC v7 | IV 期结肠癌 AJCC v7 | IV 期直肠癌 AJCC v7 | IVA 期结肠癌 AJCC v7 | IVA 期直肠癌 AJCC v7 | IVB 期结肠癌 AJCC v7 | IVB 期直肠癌 AJCC v7 | III 期结直肠癌... 及其他条件美国
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)主动,不招人IV 期结直肠癌 AJCC v8 | IVA 期结直肠癌 AJCC v8 | IVB 期结直肠癌 AJCC v8 | IVC 期结直肠癌 AJCC v8 | III 期结直肠癌 AJCC v8 | IIIA 期结直肠癌 AJCC v8 | IIIB 期结直肠癌 AJCC v8 | IIIC 期结直肠癌 AJCC v8 | 难治性结直肠癌美国