A Phase I Study of Induction Carboplatin / Paclitaxel Chemotherapy, Pre-operative Radiotherapy With Gadolinium Texaphyrin (Gd-Tex), and Surgical Resection in Stage IIIA (N2) Non-small Cell Lung Carcinoma.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose, defined as that dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT) graded according to CTC version 2.0
研究概览
简要总结
Phase I trial to study the effectiveness of combining carboplatin and paclitaxel, radiation therapy with gadolinium texaphyrin, and surgery in treating patients who have stage IIIA non-small cell lung cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as gadolinium texaphyrin may make the tumor cells more sensitive to radiation therapy. Combining chemotherapy, radiation therapy, and surgery may kill more tumor cells.
详细描述
OBJECTIVES:
I. Determine and compare the frequency and grade of toxicities with the use of gadolinium texaphyrin as a radiosensitizer at two dose levels during preoperative radiotherapy in patients with stage IIIA non-small cell lung cancer.
II. Measure the tumor, involved lymph nodes, and normal lung concentrations of gadolinium and compare to the image pixel intensity obtained by the 1.5 Tesla MRI in this patient population given this regimen.
OUTLINE: This is a dose escalation study of gadolinium texaphyrin (Gd-Tex).
Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 1-2 hours every 3 weeks for 3 courses. Three weeks after completion of induction chemotherapy, patients receive Gd-Tex IV over 30 minutes twice weekly for 10 doses during preoperative radiotherapy. Radiotherapy is administered daily 5 days a week for 5 weeks. Approximately 3.5 weeks after completion of preoperative radiotherapy, patients undergo complete surgical resection. Three hours prior to surgery, patients receive an eleventh dose of Gd-Tex if they do not develop grade 3 or 4 toxicity with the tenth dose. Patients also receive a MRI without contrast prior to surgery. If the tumor is found to be unresectable, patients may receive additional radiation and/or chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Histologically confirmed non-small cell carcinoma of the lung
- •Surgical staging with mediastinoscopy or anterior thoracotomy required
- •T1-T3, N2, M0
- •Must appear resectable
- •Performance status - Karnofsky 70-100%
- •WBC at least 3,000/mm^3
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin normal
- •AST no greater than 2.5 times upper limit of normal
- •Creatinine no greater than 2 mg/dL
- •Creatinine clearance at least 60 mL/min
- •No symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
- •FEV greater than 0.8 L
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Weight loss no greater than 10% of total body weight within past 3 months
- •No evidence of neuropathy
- •No history of allergy to platinum compounds, paclitaxel, porphyrins, or antiemetics appropriate for administration in conjunction with protocol chemotherapy
- •No concurrent uncontrolled illness (e.g., active infection)
- •No medical contraindication to MRI (e.g., pacemaker or aneurysm clip)
- •No G6PD deficiency
- •No known history of porphyria
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
- •No prior chest radiotherapy in area of tumor/nodes
- •No other concurrent investigational agents
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 1-2 hours every 3 weeks for 3 courses. Three weeks after completion of induction chemotherapy, patients receive Gd-Tex IV over 30 minutes twice weekly for 10 doses during preoperative radiotherapy. Radiotherapy is administered daily 5 days a week for 5 weeks. Approximately 3.5 weeks after completion of preoperative radiotherapy, patients undergo complete surgical resection. Three hours prior to surgery, patients receive an eleventh dose of Gd-Tex if they do not develop grade 3 or 4 toxicity with the tenth dose. Patients also receive a MRI without contrast prior to surgery. If the tumor is found to be unresectable, patients may receive additional radiation and/or chemotherapy.
干预措施: paclitaxel (Drug)
Arm I
Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 1-2 hours every 3 weeks for 3 courses. Three weeks after completion of induction chemotherapy, patients receive Gd-Tex IV over 30 minutes twice weekly for 10 doses during preoperative radiotherapy. Radiotherapy is administered daily 5 days a week for 5 weeks. Approximately 3.5 weeks after completion of preoperative radiotherapy, patients undergo complete surgical resection. Three hours prior to surgery, patients receive an eleventh dose of Gd-Tex if they do not develop grade 3 or 4 toxicity with the tenth dose. Patients also receive a MRI without contrast prior to surgery. If the tumor is found to be unresectable, patients may receive additional radiation and/or chemotherapy.
干预措施: carboplatin (Drug)
Arm I
Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 1-2 hours every 3 weeks for 3 courses. Three weeks after completion of induction chemotherapy, patients receive Gd-Tex IV over 30 minutes twice weekly for 10 doses during preoperative radiotherapy. Radiotherapy is administered daily 5 days a week for 5 weeks. Approximately 3.5 weeks after completion of preoperative radiotherapy, patients undergo complete surgical resection. Three hours prior to surgery, patients receive an eleventh dose of Gd-Tex if they do not develop grade 3 or 4 toxicity with the tenth dose. Patients also receive a MRI without contrast prior to surgery. If the tumor is found to be unresectable, patients may receive additional radiation and/or chemotherapy.
干预措施: motexafin gadolinium (Drug)
Arm I
Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 1-2 hours every 3 weeks for 3 courses. Three weeks after completion of induction chemotherapy, patients receive Gd-Tex IV over 30 minutes twice weekly for 10 doses during preoperative radiotherapy. Radiotherapy is administered daily 5 days a week for 5 weeks. Approximately 3.5 weeks after completion of preoperative radiotherapy, patients undergo complete surgical resection. Three hours prior to surgery, patients receive an eleventh dose of Gd-Tex if they do not develop grade 3 or 4 toxicity with the tenth dose. Patients also receive a MRI without contrast prior to surgery. If the tumor is found to be unresectable, patients may receive additional radiation and/or chemotherapy.
干预措施: conventional surgery (Procedure)
Arm I
Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 1-2 hours every 3 weeks for 3 courses. Three weeks after completion of induction chemotherapy, patients receive Gd-Tex IV over 30 minutes twice weekly for 10 doses during preoperative radiotherapy. Radiotherapy is administered daily 5 days a week for 5 weeks. Approximately 3.5 weeks after completion of preoperative radiotherapy, patients undergo complete surgical resection. Three hours prior to surgery, patients receive an eleventh dose of Gd-Tex if they do not develop grade 3 or 4 toxicity with the tenth dose. Patients also receive a MRI without contrast prior to surgery. If the tumor is found to be unresectable, patients may receive additional radiation and/or chemotherapy.
干预措施: radiation therapy (Radiation)
结局指标
主要结局
Maximum tolerated dose, defined as that dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT) graded according to CTC version 2.0
时间窗: Up to day 119
次要结局
- Concentrations of gadolinium in tumor, tumor involved lymph nodes, normal lung, and blood(Up to day 123)
- Image pixel intensities in tumor, tumor involved lymph nodes, normal lung, and blood obtained by 1.5 Tesla MRI(Up to day 119)