Randomized Phase II Trial of Concurrent Chemoradiotherapy +/- Metformin HCL in Locally Advanced NSCLC
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- NRG Oncology
- 入组人数
- 170
- 试验地点
- 438
- 主要终点
- Percentage of Participants Alive Without Progression (Progression-free Survival)
研究概览
简要总结
This randomized phase II trial studies how well chemotherapy and radiation therapy given with or without metformin hydrochloride works in treating patients with stage III non-small cell lung cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Metformin hydrochloride may shrink tumors and keep them from coming back. It is not yet known whether chemotherapy and radiation therapy is more effective when given with or without metformin hydrochloride in treating stage III non-small cell lung cancer.
详细描述
PRIMARY OBJECTIVES:
I. To determine whether metformin hydrochloride (MET) added to chemoradiotherapy can improve progression-free survival (PFS) in patients with locally advanced non-small cell lung cancer (NSCLC).
SECONDARY OBJECTIVES:
I. Determine the effects of MET on overall survival (OS), time to local-regional progression (LRP), and time to distant metastasis (DM).
II. Evaluate the effect of MET on chemoradiotherapy toxicity (Common Terminology Criteria for Adverse Events, version 4 [CTCAE, v. 4]) within 1 year of completion of all treatment.
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
- •Pathologically (histologically or cytologically) proven diagnosis of stage IIIA or IIIB non-small cell lung cancer within 84 days of registration; eligible histologies include adenocarcinoma, adenosquamous, large cell carcinoma, squamous carcinoma, non-lobar and non-diffuse bronchoalveolar cell carcinoma or non-small cell lung cancer not otherwise specified)
- •Patients must have measurable disease
- •Patients must have unresectable disease, be medically inoperable, or unwilling to undergo surgical management
- •Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
- •History/physical examination, including documentation of height, weight, body surface area, and vital signs, within 30 days prior to registration
- •Computed tomography (CT) with IV contrast or magnetic resonance imaging (MRI) imaging (if CT scan with contrast is medically contraindicated) of the lung and upper abdomen through the adrenal glands, required within 45 days prior to registration (recommended within 30 days prior to registration
- •MRI of the brain with contrast (or CT with contrast if MRI is medically contraindicated) within 45 days prior to registration; note: the use of intravenous contrast is required for the MRI or CT; an MRI without contrast is only permitted if the patient has a contrast allergy
- •Whole-body fludeoxyglucose (FDG)-positron emission tomography (PET)/CT required within 45 days prior to registration (recommended within 30 days prior to registration; note: patients do not need to have a separate CT of the chest and upper abdomen with contrast if PET/CT imaging includes a high quality CT with contrast
- •Zubrod performance status 0-1
- •Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
- •Complete blood count(CBC)/differential obtained within 14 days prior to registration on study, with adequate bone marrow function defined as follows:
- •Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
- •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)
- •Adequate renal function within 14 days prior to registration, defined as serum creatinine within normal institutional limits or creatinine clearance must be at least 60 ml/min;
- •Adequate hepatic function within 14 days prior to registration, defined as total bilirubin ≤ 1.5 x upper limit of normal (ULN) for the institution and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase ≤ 2.5 x ULN for the institution;
- •Fasting blood glucose ≤ 125 mg/dL within 14 days prior to registration;
- •Serum albumin > 3.0 g/dl within 14 days prior to registration;
- •For women of childbearing potential, a serum pregnancy test within 72 hours prior to registration;
- •Patients with post-obstructive pneumonia are eligible provided they no longer require intravenous antibiotics at registration;
- •Patients must be at least 3 weeks from prior thoracotomy (if performed);
- •If a pleural effusion is present, the following criteria must be met at registration to exclude malignant involvement (incurable M1a disease):
- •When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative;
- •Effusions that are minimal (i.e. not visible under ultrasound guidance) and that are too small to safely tap are eligible.
- •Women of childbearing potential and male participants must practice adequate contraception throughout the study;
排除标准
- •Patients with mixed small cell and non-small cell histologies
- •Patients with distant metastasis
- •Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 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
- •Patients currently using metformin (metformin hydrochloride), other oral hypoglycemic agents or insulin
- •Patients with any history of allergic reaction to paclitaxel or other taxanes or carboplatin
- •Patients with a history of chronic kidney disease or lactic acidosis
- •Patients with >= 10% weight loss within the past month
- •Severe, active co-morbidity, defined as follows:
- •Diagnosis of type I or type II diabetes mellitus
- •Uncontrolled neuropathy >= grade 2 regardless of cause
- •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 within 30 days of registration
- •Severe hepatic disease, defined as a diagnosis of Child-Pugh class B or C hepatic disease
- •Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol
- •End-stage renal disease (ie, on dialysis or dialysis has been recommended)
- •Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
研究组 & 干预措施
Chemoradiation
60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
干预措施: Carboplatin (Drug)
Metformin + Chemoradiation
Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
干预措施: Radiation Therapy (Radiation)
Chemoradiation
60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
干预措施: Paclitaxel (Drug)
Metformin + Chemoradiation
Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
干预措施: Carboplatin (Drug)
Chemoradiation
60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
干预措施: Radiation Therapy (Radiation)
Metformin + Chemoradiation
Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
干预措施: Metformin (Drug)
Metformin + Chemoradiation
Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Percentage of Participants Alive Without Progression (Progression-free Survival)
时间窗: From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.
Progression is defined per RECIST v1.1 as change in a known lesion(s) meeting one of the following criteria: \[1\] At least a 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be \> 5 mm. \[2\] Appearance of ≥1 new lesions. Progression-free survival time is defined as time from randomization to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.
次要结局
- Percentage of Participants With Distant Metastases(From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.)
- Percentage of Participants With Treatment-related Grade 3 or Higher Adverse Events(From start of treatment to last follow-up. Maximum follow-up at time of analysis was 47.2 months.)
- Percentage of Participants Alive (Overall Survival)(From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.)
- Percentage of Participants With Local-regional Progression(From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.)