A Randomized Phase II Study of Individualized Combined Modality Therapy for Stage III Non-small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 59
- 试验地点
- 173
- 主要终点
- Progression-free Survival
研究概览
简要总结
This randomized phase II trial studies how well erlotinib hydrochloride or crizotinib with chemoradiation therapy works in treating patients with stage III non-small cell lung cancer. Radiation therapy uses high energy x rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin, etoposide, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving erlotinib hydrochloride is more effective than crizotinib with chemoradiation therapy in treating patients with non-small cell lung cancer.
详细描述
PRIMARY OBJECTIVES:
I. To assess whether patients with unresectable local-regionally advanced non-small cell lung cancer (NSCLC) treated with targeted agents based on molecular characteristics have a longer progression-free survival than those treated with standard care therapy alone.
SECONDARY OBJECTIVES:
I. To evaluate response rate. II. To assess toxicity. III. To assess overall survival. IV. To correlate clinical outcomes with tumor molecular aberrations identified from deep sequencing of selected kinomes in patients from whom adequate baseline tissue is available.
OUTLINE: Eligible patients are assigned to one of two cohorts based on pre-enrollment screening by the enrolling institution for two biomarkers: EGFR TK mutation and EML4-ALK fusion arrangement. Within each cohort, patients are randomized to either an experimental or control arm, resulting in a total of four treatment arms overall. Patients with both the EGFR mutation and ALK arrangement are placed in the ALK Cohort.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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 or cytologically confirmed, newly diagnosed non-squamous NSCLC
- •Unresectable stage IIIA or IIIB disease; patients must be surgically staged to confirm N2 or N3 disease; patients may have invasive mediastinal staging by mediastinoscopy, mediastinotomy, endobronchial ultrasound transbronchial aspiration (EBUS-TBNA), endoscopic ultrasound (EUS), or video-assisted thoracoscopic surgery (VATS)
- •Patients with any tumor (T) with node (N)2 or N3 are eligible; patients with T3, N1-N3 disease are eligible if deemed unresectable; patients with T4, any N are eligible
- •Patients must have measurable disease, i.e., lesions that can be accurately measured in at least 1 dimension (longest dimension in the plane of measurement is to be recorded) with a minimum size of 10 mm by computed tomography (CT) scan (CT scan slice thickness no greater than 5 mm)
- •Patients with a pleural effusion, which is a transudate, cytologically negative and non-bloody, are eligible if the radiation oncologist feels the tumor can be encompassed within a reasonable field of radiotherapy
- •If a pleural effusion can be seen on the chest CT but not on chest x-ray and is too small to tap, the patient will be eligible; patients who develop a new pleural effusion after thoracotomy or other invasive thoracic procedure will be eligible
- •The institution's pre-enrollment biomarker screening at a Clinical Laboratory Improvement Amendments (CLIA) certified lab documents presence of known "sensitive" mutations in epidermal growth factor receptor tyrosine kinase (EGFR TK) domain (exon 19 deletion, L858) and/or EML4-anaplastic lymphoma kinase (ALK) fusion arrangement; either the primary tumor or the metastatic lymph node tissue may be used for testing of mutations
- •The institution's pre-enrollment biomarker screening at a CLIA certified lab documents absence of T790M mutation in the EGFR TK domain
- •Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
- •History/physical examination, including recording of pulse, blood pressure (BP), weight, and body surface area, within 45 days prior to registration
- •Whole body fludeoxyglucose-positron emission tomography (FDG-PET)/CT (orbits to mid-thighs) within 30 days prior to registration; PET/CT must be negative for distant metastasis
- •CT scan with contrast of the chest and upper abdomen to include liver and adrenals (unless medically contraindicated) within 30 days prior to registration
- •Magnetic resonance imaging (MRI) of the brain with contrast (or CT scan with contrast, if MRI medically contraindicated) within 30 days prior to registration
- •Zubrod performance status 0-1 within 14 days prior to registration
- •Absolute neutrophil count (ANC) >= 1,000 cells/mm^3
- •Platelets >= 100,000 cells/mm^3
- •Hemoglobin >= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
- •Serum creatinine < 1.5 mg/dL or calculated creatinine clearance >= 50 ml/min (by Cockcroft-Gault formula) within 14 days prior to registration
- •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) within 14 days prior to registration
- •Bilirubin within normal institutional limits within 14 days prior to registration
- •Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential
- •Patient must provide study specific informed consent prior to study entry, including consent for mandatory screening of tissue
排除标准
- •Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 730 days (2 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
- •Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
- •Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
- •Atelectasis of the entire lung
- •Contralateral hilar node involvement
- •Exudative, bloody, or cytologically malignant effusions
- •Severe, active co-morbidity, defined as follows:
- •Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
- •Transmural myocardial infarction within the last 6 months
- •Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- •Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
- •Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients
- •Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
- •Prior allergic reaction to the study drug(s) involved in this protocol
研究组 & 干预措施
EGFR: Erlotinib
Induction erlotinib for 12 weeks followed by chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy. Patients who have had no response (partial or complete) after 6 weeks of induction therapy start chemoradiation therapy immediately.
干预措施: Radiation Therapy (Radiation)
EGFR: Erlotinib
Induction erlotinib for 12 weeks followed by chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy. Patients who have had no response (partial or complete) after 6 weeks of induction therapy start chemoradiation therapy immediately.
干预措施: Carboplatin (Drug)
EGFR: Erlotinib
Induction erlotinib for 12 weeks followed by chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy. Patients who have had no response (partial or complete) after 6 weeks of induction therapy start chemoradiation therapy immediately.
干预措施: Cisplatin (Drug)
EGFR: Erlotinib
Induction erlotinib for 12 weeks followed by chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy. Patients who have had no response (partial or complete) after 6 weeks of induction therapy start chemoradiation therapy immediately.
干预措施: Erlotinib (Drug)
EGFR: Erlotinib
Induction erlotinib for 12 weeks followed by chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy. Patients who have had no response (partial or complete) after 6 weeks of induction therapy start chemoradiation therapy immediately.
干预措施: Etoposide (Drug)
EGFR: Erlotinib
Induction erlotinib for 12 weeks followed by chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy. Patients who have had no response (partial or complete) after 6 weeks of induction therapy start chemoradiation therapy immediately.
干预措施: Paclitaxel (Drug)
EGFR: No Erlotinib
Chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy.
干预措施: Radiation Therapy (Radiation)
EGFR: No Erlotinib
Chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy.
干预措施: Carboplatin (Drug)
EGFR: No Erlotinib
Chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy.
干预措施: Cisplatin (Drug)
EGFR: No Erlotinib
Chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy.
干预措施: Etoposide (Drug)
EGFR: No Erlotinib
Chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy.
干预措施: Paclitaxel (Drug)
ALK: Crizotinib
Induction crizotinib for 12 weeks followed by chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy. Patients who have had no response (partial or complete) after 6 weeks of induction therapy start chemoradiation therapy immediately.
干预措施: Radiation Therapy (Radiation)
ALK: Crizotinib
Induction crizotinib for 12 weeks followed by chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy. Patients who have had no response (partial or complete) after 6 weeks of induction therapy start chemoradiation therapy immediately.
干预措施: Carboplatin (Drug)
ALK: Crizotinib
Induction crizotinib for 12 weeks followed by chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy. Patients who have had no response (partial or complete) after 6 weeks of induction therapy start chemoradiation therapy immediately.
干预措施: Cisplatin (Drug)
ALK: Crizotinib
Induction crizotinib for 12 weeks followed by chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy. Patients who have had no response (partial or complete) after 6 weeks of induction therapy start chemoradiation therapy immediately.
干预措施: Crizotinib (Drug)
ALK: Crizotinib
Induction crizotinib for 12 weeks followed by chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy. Patients who have had no response (partial or complete) after 6 weeks of induction therapy start chemoradiation therapy immediately.
干预措施: Etoposide (Drug)
ALK: Crizotinib
Induction crizotinib for 12 weeks followed by chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy. Patients who have had no response (partial or complete) after 6 weeks of induction therapy start chemoradiation therapy immediately.
干预措施: Paclitaxel (Drug)
ALK: No Crizotinib
Chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy.
干预措施: Radiation Therapy (Radiation)
ALK: No Crizotinib
Chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy.
干预措施: Carboplatin (Drug)
ALK: No Crizotinib
Chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy.
干预措施: Cisplatin (Drug)
ALK: No Crizotinib
Chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy.
干预措施: Etoposide (Drug)
ALK: No Crizotinib
Chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Progression-free Survival
时间窗: From randomization to study termination. Maximum follow-up was 39.0 months
Progression is defined using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST) guideline v1.1 as a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions at any location. Progression-free survival time is measured from the date of randomization to the date of first progression, death, or last known follow-up (censored). No statistical testing was done due to early study termination.
次要结局
- Percentage of Patients With Complete or Partial Response(From randomization to study termination. Maximum follow-up was 39.0 months)
- Number of Patients With Grade 3-5 Adverse Events(From randomization to study termination. Maximum follow-up was 39.0 months)
- Correlation Between Clinical Outcomes and Tumor Molecular Aberrations(Baseline)
- Overall Survival(From randomization to study termination. Maximum follow-up was 39.0 months)
- Distant Progression-free Survival(From randomization to study termination. Maximum follow-up was 39.0 months)
- Local-regional Progression-free Survival(From randomization to study termination. Maximum follow-up was 39.0 months)