Sunitinib and Erlotinib in Treating Patients With Unresectable or Metastatic Kidney Cancer
A Dose Escalation Phase II Study of Sunitinib Plus Erlotinib in Advanced Renal Carcinoma
RATIONALE: Sunitinib and erlotinib may stop the growth of tumor cell by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sunitinib together with erlotinib may kill more tumor cells.
PURPOSE: This phase II trial is studying the best dose of erlotinib when given together with sunitinib and to see how well they work in treating patients with unresectable or metastatic kidney cancer.
研究概览
详细说明
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of erlotinib hydrochloride when administered with sunitinib malate in patients with unresectable or metastatic renal cell carcinoma.
- Determine the 8-month progression-free survival of patients treated with this regimen.
Secondary
- Determine the safety of sunitinib malate and erlotinib hydrochloride in these patients.
- Determine the duration of response in these patients.
- Determine the proportion of patients whose best overall response is complete response, partial response, stable disease, or progressive disease.
- Determine the overall survival of patients treated with this regimen.
- Determine the maximum percent reduction in tumor measurement in patients treated with this regimen.
- Collect blood and tissue from these patients for future correlative studies.
OUTLINE: This is an open-label, multicenter, dose-escalation study of erlotinib hydrochloride.
Patients receive oral sunitinib malate once daily on days 1-28 and oral erlotinib hydrochloride once daily on days 1-42. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 33% of patients experience dose-limiting toxicity. Once the MTD is determined, patients are treated with erlotinib hydrochloride at the MTD and sunitinib malate.
Patients undergo blood and tumor specimen collection periodically during study for future correlative studies.
PROJECTED ACCRUAL: A total of 49 patients will be accrued for this study.
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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California
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Los Angeles、California、美国、90033
- University of Southern California
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Oregon
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Portland、Oregon、美国、97213-2967
- Providence Cancer Center at Providence Portland Medical Center
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Portland、Oregon、美国、97239-3098
- OHSU Knight Cancer Institute
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Salem、Oregon、美国、97301
- Salem Hospital
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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
DISEASE CHARACTERISTICS:
Histologically confirmed renal cell carcinoma with a component of clear cell or papillary carcinoma
- Unresectable or metastatic disease (radiologically or clinically confirmed)
- Measurable disease (≥ 1 site)
- No known brain metastasis that has not been adequately treated with radiotherapy and/or surgery
PATIENT CHARACTERISTICS:
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- No grade 3 hemorrhage within the past 4 weeks
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 times ULN (< 5 times ULN if due to underlying disease)
- No chronic liver disease (i.e., chronic active hepatitis or cirrhosis)
- Creatinine ≤ 1.5 times ULN
None of the following cardiovascular conditions within the past 12 months:
- Myocardial infarction
- Severe/unstable angina
- Coronary/peripheral artery bypass graft
- Symptomatic congestive heart failure
- Cerebrovascular accident or transient ischemic attack
- Pulmonary embolism
- Ongoing cardiac dysrhythmia ≥ grade 2
- Atrial fibrillation of any grade
- Prolongation of the corrected QT (QTc) interval to > 450 msec for males or to > 470 msec for females
- Left Ventricular Ejection Fraction (LVEF) normal by Multigated Acquisition (MUGA) or echocardiogram
- No hypertension uncontrolled with medical therapy
- No other active malignancy within the past 5 years except basal cell skin cancer or cervical carcinoma in situ
- No uncontrolled adrenal insufficiency
- No uncontrolled hypothyroidism
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after completion of study treatment
- No severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection)
- No impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs
- No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- More than 4 weeks since prior major surgery
- More than 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin C)
- More than 4 weeks since prior radiotherapy
- No prior radiotherapy to > 25% of the bone marrow
- More than 28 days since prior investigational agents
- No prior sunitinib malate
- No prior anti-epidermal growth factor receptor therapy (e.g., erlotinib hydrochloride, panitumumab, cetuximab, or gefitinib)
No concurrent therapeutic warfarin
- Low-dose oral warfarin ≤ 2 mg daily for deep vein thrombosis prophylaxis is allowed after the maximum tolerated dose of erlotinib hydrochloride is determined
- No concurrent Hypericum perforatum (St. John's wort)
- No concurrent chemotherapy or biologic therapy
- No other concurrent anticancer therapy
- No other concurrent investigational agents
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 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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实验性的:Erlotinib and Sunitinib
Drug: erlotinib hydrochloride Dose Level 0 = 50 mg/day, continuous daily; 0.5= 75 mg/day, continuous daily;
Drug: sunitinib malate Will be administered at 50 mg daily, 4 weeks on, 2 weeks off |
Dose Level 0 = 50 mg/day, continuous daily; 0.5= 75 mg/day, continuous daily;
Will be administered at 50 mg daily, 4 weeks on, 2 weeks off
Paraffin block (or unstained slides) of the primary tumor and/or metastatic lesions (as available) and a plasma sample for future correlative studies will be collected.
A paraffin block (or at least 10 unstained slides, each of 10 micromillimeter thickness) from the original paraffin-embedded biopsy material taken at the diagnosis will be stored at 4 degrees Celsius.
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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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Maximum Tolerated Dose (MTD) of Erlotinib Hydrochloride When Used in Combination With Sunitinib.
大体时间:Participants assessed for DLTs weekly during the first cycle of treatment and every 3 weeks in subsequent cycles until at least one DLT occurs in 33% or more of participants at that dose; participants assessed for the duration of the study, up to 7 years
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The MTD is defined as the dose that produces dose limiting toxicity (DLT) in 33% of the patients.
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Participants assessed for DLTs weekly during the first cycle of treatment and every 3 weeks in subsequent cycles until at least one DLT occurs in 33% or more of participants at that dose; participants assessed for the duration of the study, up to 7 years
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Progression-free Survival at 8 Months
大体时间:8 months after initiating treatment with sunitinib in combination with erlotinib in patients with metastatic or unresectable clear cell or papillary carcinoma of the kidney
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Defined as the proportion of patients who are progression free (CR, PR and SD) at 8 months after initiating treatment with sunitinib in combination with erlotinib in patients with metastatic or unresectable clear cell or papillary carcinoma of the kidney.
Complete Response (CR)= disappearance of all target lesions, Partial Response (PR)= At least a 30% decrease in the sum of the longest diameter of target lesions, and Stable Disease (SD)= Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (20% increase in the sum).
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8 months after initiating treatment with sunitinib in combination with erlotinib in patients with metastatic or unresectable clear cell or papillary carcinoma of the kidney
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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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To Determine the Safety of Sunitinib in Combination With Erlotinib
大体时间:For the duration of the study, up to 7 years
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For the duration of the study, up to 7 years
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Median Time to Progression
大体时间:For the duration of the study, up to 7 years
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The Kaplan-Meier method will be used to estimate the median time to progression.
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For the duration of the study, up to 7 years
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Proportion of Patients Whose Best Overall Response is Complete Response, Partial Response, Stable Disease, or Progressive Disease
大体时间:From the start of treatment until the criteria for response is met.
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From the start of treatment until the criteria for response is met.
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Maximum Percent Change in Tumor Measurement
大体时间:Baseline through end of study, up to 7 years
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The maximum percent change in Tumor Measurement is the greatest percent change in longest diameter (LD) for the target lesions from the baseline LD.
For patients with no change in LD, the maximum percent change is the lowest increase in LD from the baseline LD.
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Baseline through end of study, up to 7 years
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合作者和调查者
调查人员
- 学习椅:Christopher W. Ryan, MD、OHSU Knight Cancer Institute
出版物和有用的链接
一般刊物
- Ryan CW, Curti BD, Pattee KJ, et al.: A dose-escalation phase II study of sunitinib (S) plus erlotinib (E) in advanced renal carcinoma (RCC). [Abstract] American Society of Clinical Oncology 2008 Genitourinary Cancers Symposium, Feb 14-16, 2008, San Francisco, CA. A-361, 2008.
- Feng Z, Curti BD, Quinn DI, Strother JM, Chen Z, Agnor R, Beer TM, Ryan CW. A Phase II, Single-arm Trial of Sunitinib and Erlotinib in Advanced Renal Cell Carcinoma. Clin Genitourin Cancer. 2022 Oct;20(5):415-422. doi: 10.1016/j.clgc.2022.04.018. Epub 2022 May 5.
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 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- CDR0000526204
- P30CA069533 (美国 NIH 拨款/合同)
- OHSU-2683 (其他标识符:Oregon Health & Science University IRB)
- OHSU-SOL-06051-LM (其他标识符:OHSU Knight Cancer Institute)
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.
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