Erlotinib, Paclitaxel, and Carboplatin Combined With Radiation Therapy for Stage III Non-Small Cell Lung Cancer
A Phase I/II Trial of Neoadjuvant Paclitaxel, Carboplatin and OSI-774 (Tarceva) With Concurrent Accelerated Hyperfractionation Radiation Followed by Maintenance Therapy With OSI-774 for Stage III Non-Small Cell Lung Cancer
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving erlotinib, paclitaxel, and carboplatin together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase I/II trial is studying the best dose of erlotinib and the side effects of erlotinib, paclitaxel, and carboplatin when given together with radiation therapy and to see how well they work in treating patients who are undergoing surgery for stage III non-small cell lung cancer.
研究概览
详细说明
OBJECTIVES:
Primary
- Assess the safety and feasibility of erlotinib hydrochloride, paclitaxel, and carboplatin in combination with accelerated hyperfractionated radiotherapy in patients with stage IIIA or IIIB non-small cell lung cancer.
- Determine the maximum tolerated dose and recommended phase II dose of erlotinib hydrochloride in these patients.
- Assess the safety and tolerability of long-term maintenance erlotinib hydrochloride after completion of adjuvant chemoradiotherapy in these patients.
Secondary
- Evaluate the clinical and pathological response rate in these patients after neoadjuvant erlotinib hydrochloride, paclitaxel, carboplatin, and radiotherapy.
- Assess the impact of erlotinib hydrochloride on disease-free survival, overall survival, locoregional control, and distant metastatic control in these patients.
OUTLINE: This is an open-label, phase I dose-escalation study of erlotinib hydrochloride followed by a non-randomized phase II study.
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 preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Phase I:
- Neoadjuvant chemoradiotherapy: Patients receive oral erlotinib hydrochloride once daily on days 1-28 and paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, and 15 in the absence of disease progression or unacceptable toxicity. Patients concurrently undergo radiotherapy twice daily on days 1-5 and 8-12. Patients with complete response, partial response, or stable disease proceed to surgery. Patients who develop a medical contraindication to surgery (i.e., medically unresectable) receive a second course of erlotinib hydrochloride, paclitaxel, carboplatin, and radiotherapy as above within 2 weeks after completion of neoadjuvant chemoradiotherapy.
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 preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Surgery: Within 4 weeks after completion of neoadjuvant chemoradiotherapy, patients undergo surgical resection and then proceed to adjuvant chemoradiotherapy.
- Adjuvant chemoradiotherapy: Within 6-8 weeks after surgery, patients receive a second course of erlotinib hydrochloride, paclitaxel, carboplatin, and radiotherapy as in neoadjuvant chemoradiotherapy.
Maintenance therapy: All patients receive oral erlotinib hydrochloride once daily for 2 years in the absence of disease progression or unacceptable toxicity.
- Phase II: Patients receive treatment as in phase I with erlotinib hydrochloride at the MTD.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.
研究类型
注册 (实际的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
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Ohio
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Cleveland、Ohio、美国、44195
- Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
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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 or cytologically confirmed non-small cell lung cancer
- Surgically determined stage IIIA or IIIB disease
Histology from an involved mediastinal or supraclavicular lymph nodes alone will be allowed if a separate distal primary lesion is clearly evident on radiographs
- Histological or cytological proof of mediastinal nodal involvement by mediastinoscopy, Chamberlain procedure, thoracoscopy, thoracotomy, or CT-guided biopsy is required except for cases of paralysis of left true vocal cord with separate left lung primary distinct from enlarged nodes > 1 cm in the anterior-posterior window seen on the CT scan
- Patients with N3 or T4 status must be evaluated and deemed potentially resectable after induction chemotherapy and radiation therapy
- Measurable and evaluable disease
- No malignant pleural effusion except for effusion visible only on CT scan and deemed too small to tap
- No pericardial effusion
- No small or mixed small cell/non-small cell lung cancer
- No massive lesions requiring radiation to the entire lung
- No metastatic cancer to the lungs
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- WBC ≥ 3,000/mm^3
- Platelet count > 100,000/mm^3
- Serum creatinine ≤ 2.0 mg/dL
- Alkaline phosphatase, AST, and ALT < 2 times upper limit of normal
- Albumin > 3.0 g/dL
- Serum bilirubin < 1.5 mg/dL
- Adequate pulmonary function
- No clinical evidence of another uncontrolled malignancy
- No requirement for urgent therapy for severe local symptoms such as post-obstructive pneumonia
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy, radiation therapy, or immunotherapy for lung cancer
- No prior surgery to treat the cancer
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：顺序分配
- 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：Dose Level A
Erlotinib, Paclitaxel, and Carboplatin with Radiation Dose Level A: 50 mg OSI-774/50 mg/m2 Paclitaxel/2 AUC Carboplatin |
常规手术
AUC2 weekly x 3 weeks
其他名称：
Daily
其他名称：
50mg/m2/weekly x 3 weeks
150 cGy bid
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|
实验性的：Dose Level B
Erlotinib, Paclitaxel, and Carboplatin with Radiation Dose Level B: 100 mg OSI-774/50 mg/m2 Paclitaxel/2 AUC Carboplatin |
常规手术
AUC2 weekly x 3 weeks
其他名称：
Daily
其他名称：
50mg/m2/weekly x 3 weeks
150 cGy bid
|
|
实验性的：Dose Level C
Erlotinib, Paclitaxel, and Carboplatin with Radiation Dose Level C: 150 mg OSI-774/50 mg/m2 Paclitaxel/2 AUC Carboplatin |
常规手术
AUC2 weekly x 3 weeks
其他名称：
Daily
其他名称：
50mg/m2/weekly x 3 weeks
150 cGy bid
|
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 of Erlotinib Hydrochloride (Phase I)
大体时间：2 weeks after surgery
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The Phase I portion of this study is to determine the Maximum Tolerated Dose (MTD) of combining OSI-774 with the paclitaxel-carboplatin chemoradiation protocol and to assess the safety and feasiblity of this combination.
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2 weeks after surgery
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Tolerability of Long-term OSI-774 (Phase II)
大体时间：2 years
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Number of patients who experienced grade >/= 3 toxicities on maintanance erolotinib (OSI-774)
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2 years
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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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Pathological Complete Response Rate
大体时间：2 years
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Number of participants with an pathological complete response rate using the RECIST criteria. Complete response: Disappearance of all measurable and evaluable disease Partial response: A 30% or greater decline in the sum of the longest diameter of target lesions compared to the baseline measurement. Progressive disease: A 20% or greater increase in the sum of the longest diameter of the target lesions compared to the baseline. Stable disease: Disease that did not meet the criteria for a CR / PR or progressive disease. |
2 years
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Overall Survival
大体时间：3 years
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Percent of participants still alive from the date of study entry to the date of the corresponding event (recurrence of death) or the date of final follow-up.
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3 years
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Progression Free Survival (PFS)
大体时间：3 years
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Months from the date of study entry to the date of the corresponding event (recurrence of death) or the date of final follow-up
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3 years
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Locoregional Control
大体时间：2 years
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Estimated by the Kaplan-Meier method and summarized at various follow-up points as the number of patients remaining at risk, the event estimate, standard error, and median.From the date of study entry to the date of the corresponding event (recurrence of death) or the date of final follow-up, assessed up to 2 years
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2 years
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Distant Control
大体时间：2 years
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Estimated by the Kaplan-Meier method and summarized at various follow-up points as the number of patients remaining at risk, the event estimate, standard error, and median.From the date of study entry to the date of the corresponding event (recurrence of death) or the date of final follow-up, assessed up to 2 years
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2 years
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合作者和调查者
调查人员
- 学习椅：Nathan Pennell, MD、Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
出版物和有用的链接
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
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.
常规手术的临床试验
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St. Joseph's Healthcare HamiltonHamilton Academic Health Sciences Organization完全的
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Seoul National University HospitalJohnson & Johnson Medical Companies完全的