A Phase II Trial Of Neoadjuvant Therapy With Concurrent Chemotherapy And High Dose Radiotherapy Followed By Surgical Resection And Consolidative Therapy For Locally Advanced Non-Small Cell Lung Carcinoma
概览
- 阶段
- 2 期
- 干预措施
- Induction Carboplatin
- 疾病 / 适应症
- Lung Cancer
- 发起方
- Radiation Therapy Oncology Group
- 入组人数
- 60
- 试验地点
- 22
- 主要终点
- Mediastinal Nodal Clearance Rate
- 状态
- 已完成
- 最后更新
- 6年前
概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in 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. Giving paclitaxel and carboplatin together with radiation therapy before surgery may shrink the tumor so that it can be removed. Giving chemotherapy after surgery may kill any tumor cells remaining after surgery.
PURPOSE: This phase II trial is studying how well giving paclitaxel and carboplatin together with radiation therapy works in treating patients who are undergoing surgery for stage III non-small cell lung cancer.
详细描述
OBJECTIVES: * Determine the mediastinal node clearance rate in patients with stage IIIA or IIIB non-small cell lung cancer treated with neoadjuvant induction chemoradiotherapy comprising paclitaxel, carboplatin, and high-dose radiotherapy followed by surgical resection for patients found to be resectable and consolidative chemotherapy comprising paclitaxel and carboplatin. * Determine the rate of complete pathological response in patients treated with this regimen. * Determine the feasibility of surgical resection after neoadjuvant induction chemoradiotherapy in these patients. * Determine disease-free and overall survival of patients treated with this regimen. * Determine the toxicity of this regimen in these patients.
研究者
入排标准
入选标准
- •Patients with Stage IIIA (T1-3 N2) or Stage IIIB (N3, excluding supraclavicular involvement) non-small cell lung cancer documented by biopsy or cytology (Pancoast tumors are eligible if pathologic evidence of mediastinal nodal disease is present);
- •Disease must be measurable;
- •Mediastinal lymph nodes must be proven positive by pathologic review. All patients must undergo mediastinoscopy, thoracoscopy, Chamberlain procedure, or transbronchial needle aspirate to evaluate extent of nodal involvement. Any lymph node assessed by mediastinoscopy and found to be positive will be defined as N2 disease;
- •Patients ≥ 18 years of age;
- •Life expectancy ≥ 6 months;
- •Zubrod performance status 0- 1 (See Appendix II);
- •Pretreatment laboratory values must be as follows: White blood cell count (WBC) count: ≥ 3,000/mm\^3; Absolute granulocyte count: ≥ 1,500/mm\^3; Platelets: ≥ 100,000/mm3; Total bilirubin: ≤ 1.5 x institutional upper limit of normal (ULN); Serum creatinine: ≤ 1.5 x institutional ULN; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x institutional ULN; serum albumin: ≥ 3.0 g/dL
- •Baseline forced expiratory volume (FEV1) must be at least 2.0 liters; if less than 2.0 then V/Q scan is required and projected post-operative FEV1 must be \> 800 cc based on the following formula using the quantitative Ventilation/perfusion (V/Q) scan: FEV1 = FEV1 x % perfusion to uninvolved lung from quantitative lung V/Q scan report.
- •Patient evaluation and acceptance by thoracic surgery, medical oncology, and radiation oncology; patient must be a potential surgical candidate prior to the initiation of therapy;
- •Women of childbearing potential and male participants must practice an effective method of contraception during the study;
排除标准
- •Small cell lung cancer; distant metastatic disease;
- •Evidence of clinical or radiographic supraclavicular lymph node involvement;
- •Bronchioalveolar carcinoma with lobar or multilobar involvement;
- •Unintentional weight loss \> 5% within 6 months prior to study entry, or Zubrod performance status 2 or greater;
- •Primary tumor location prevents delivery of 60 Gy and simultaneously limiting spinal cord dose to 48 Gy;
- •Patients with malignant pleural effusion;
- •Clinically evident superior vena cava syndrome;
- •Prior systemic chemotherapy or radiation therapy to the thorax;
- •Patients with known hypersensitivity to Cremophor EL;
- •Patients receiving other investigational therapy;
研究组 & 干预措施
Chemoradiation, Surgery, Chemotherapy
Induction paclitaxel(50 mg/m2 I.V. in a one-hour infusion) and induction carboplatin (AUC 2.0 I.V. in a thirty-minute infusion): 1x/week for 6 weeks. Concurrent radiation therapy (RT): 1.8 Gy/day, 5 fx/week, for a total of 50.4 Gy in 28 fractions plus a boost of 1.8 Gy/day, 5 fx/week, for a total of 10.8 Gy in 6 fractions. Followed by an assessment to determine whether patient will undergo a resection or not. Followed by consolidation paclitaxel (200 mg/m2 I.V. over three hours) and consolidation carboplatin (AUC 6.0 over one hour) q 21 days x 2.
干预措施: Induction Carboplatin
Chemoradiation, Surgery, Chemotherapy
Induction paclitaxel(50 mg/m2 I.V. in a one-hour infusion) and induction carboplatin (AUC 2.0 I.V. in a thirty-minute infusion): 1x/week for 6 weeks. Concurrent radiation therapy (RT): 1.8 Gy/day, 5 fx/week, for a total of 50.4 Gy in 28 fractions plus a boost of 1.8 Gy/day, 5 fx/week, for a total of 10.8 Gy in 6 fractions. Followed by an assessment to determine whether patient will undergo a resection or not. Followed by consolidation paclitaxel (200 mg/m2 I.V. over three hours) and consolidation carboplatin (AUC 6.0 over one hour) q 21 days x 2.
干预措施: Induction Paclitaxel
Chemoradiation, Surgery, Chemotherapy
Induction paclitaxel(50 mg/m2 I.V. in a one-hour infusion) and induction carboplatin (AUC 2.0 I.V. in a thirty-minute infusion): 1x/week for 6 weeks. Concurrent radiation therapy (RT): 1.8 Gy/day, 5 fx/week, for a total of 50.4 Gy in 28 fractions plus a boost of 1.8 Gy/day, 5 fx/week, for a total of 10.8 Gy in 6 fractions. Followed by an assessment to determine whether patient will undergo a resection or not. Followed by consolidation paclitaxel (200 mg/m2 I.V. over three hours) and consolidation carboplatin (AUC 6.0 over one hour) q 21 days x 2.
干预措施: Resection
Chemoradiation, Surgery, Chemotherapy
Induction paclitaxel(50 mg/m2 I.V. in a one-hour infusion) and induction carboplatin (AUC 2.0 I.V. in a thirty-minute infusion): 1x/week for 6 weeks. Concurrent radiation therapy (RT): 1.8 Gy/day, 5 fx/week, for a total of 50.4 Gy in 28 fractions plus a boost of 1.8 Gy/day, 5 fx/week, for a total of 10.8 Gy in 6 fractions. Followed by an assessment to determine whether patient will undergo a resection or not. Followed by consolidation paclitaxel (200 mg/m2 I.V. over three hours) and consolidation carboplatin (AUC 6.0 over one hour) q 21 days x 2.
干预措施: Consolidation Carboplatin
Chemoradiation, Surgery, Chemotherapy
Induction paclitaxel(50 mg/m2 I.V. in a one-hour infusion) and induction carboplatin (AUC 2.0 I.V. in a thirty-minute infusion): 1x/week for 6 weeks. Concurrent radiation therapy (RT): 1.8 Gy/day, 5 fx/week, for a total of 50.4 Gy in 28 fractions plus a boost of 1.8 Gy/day, 5 fx/week, for a total of 10.8 Gy in 6 fractions. Followed by an assessment to determine whether patient will undergo a resection or not. Followed by consolidation paclitaxel (200 mg/m2 I.V. over three hours) and consolidation carboplatin (AUC 6.0 over one hour) q 21 days x 2.
干预措施: Radiation Therapy
Chemoradiation, Surgery, Chemotherapy
Induction paclitaxel(50 mg/m2 I.V. in a one-hour infusion) and induction carboplatin (AUC 2.0 I.V. in a thirty-minute infusion): 1x/week for 6 weeks. Concurrent radiation therapy (RT): 1.8 Gy/day, 5 fx/week, for a total of 50.4 Gy in 28 fractions plus a boost of 1.8 Gy/day, 5 fx/week, for a total of 10.8 Gy in 6 fractions. Followed by an assessment to determine whether patient will undergo a resection or not. Followed by consolidation paclitaxel (200 mg/m2 I.V. over three hours) and consolidation carboplatin (AUC 6.0 over one hour) q 21 days x 2.
干预措施: Consolidation Paclitaxel
结局指标
主要结局
Mediastinal Nodal Clearance Rate
时间窗: At completion of concurrent chemotherapy and radiation therapy, up to 14 weeks.
If at least 12 of the first 21 evaluable patients and at least 27 of the the first 45 evaluable patients have mediastinal nodal clearance (MNC), then a conclusion of a 70% MNC rate (compared to 50%) is made using Simon's two-stage design with 90% power and 10% type I error.
次要结局
- Overall Survival at Two Years(From registration to two years)
- Percentage of Patients With Complete Pathological Response After Concurrent Chemotherapy and Radiation Therapy(At time of surgery (16-18 weeks))
- Progression-free Survival at Two Years(From registration to two years)
- Percentage of Patients Able to Undergo Surgical Resection(At time of surgery (16-18 weeks))
- Distribution of R0, R1, and R2 Resections After Chemotherapy(At time of surgery (16-18 weeks))
- Percentage of Patients With Major Surgical Morbidities Within 30 Days of Surgery(From 0 to 30 days following surgery (surgery occurs within 16-18 weeks after registration))
- Distribution of Highest Grade Adverse Event(From start of treatment to end of follow-up, a maximum of 64.3 months)