Comparing Impact of Treatment Before or After Surgery in Patients With Stage II-IIIB Resectable Non-small Cell Lung Cancer
- Conditions
- Resectable Lung Non-Small Cell CarcinomaStage II Lung Cancer AJCC v8Stage IIIA Lung Cancer AJCC v8Stage IIIB Lung Cancer AJCC v8
- Interventions
- Procedure: Surgical ProcedureProcedure: Computed TomographyProcedure: Magnetic Resonance ImagingProcedure: Positron Emission Tomography
- Registration Number
- NCT06632327
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
This phase III trial compares standard therapy given after surgery (adjuvant) to standard therapy given before and after surgery (perioperative) in treating patients with stage II-IIIB non-small cell lung cancer (NSCLC) that can be removed by surgery (resectable). The usual approach for patients with resectable NSCLC is chemotherapy and/or immunotherapy before surgery, after surgery, or both before and after surgery. This study is being done to find out which approach is better at treating patients with lung cancer. Treatment will be administered according to the current standard of care at the time of enrollment. Chemotherapy options may include cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and vinorelbine at standard doses according to the treating physician. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make deoxyribonucleic acid (DNA) and may kill tumor cells. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells. Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Other chemotherapy drugs, such as vinorelbine, 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 . Immunotherapy with monoclonal antibodies, such as nivolumab, pembrolizumab, and atezolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Starting treatment with chemotherapy and immunotherapy prior to surgery and continuing treatment after surgery may be a more effective treatment option than adjuvant therapy alone in patients with stage II-IIIB resectable NSCLC.
- Detailed Description
The primary and secondary objectives of the study:
PRIMARY OBJECTIVE:
I. To compare the 3-year real-world event-free survival (rwEFS) rate and overall survival (OS) between perioperative and adjuvant immunotherapy-based treatment for patients with resectable non-small cell lung cancer (dual endpoints).
SECONDARY OBJECTIVES:
I. To compare the rates of surgical resection between the two arms. II. To compare the rates of complete resection (R0) between the two arms. III. To summarize and compare rates of adverse events (AEs) resulting in permanent treatment discontinuation, hospitalization, or death between the two arms.
IV. To evaluate the association between locally defined pathological complete response (pCR) and rwEFS in patients randomized to the perioperative arm (arm 2).
V. To compare the rwEFS post 3-years from randomization between the two arms among patients who do not experience an event by 3 years.
EXPLORATORY OBJECTIVES:
I. To compare outcomes according to the systemic therapy administered on each arm.
II. To compare the sites of relapse between the two treatment arms.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1:
SURGERY: Patients undergo surgery within 28 days of registration.
ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines.
ARM 2:
NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines.
SURGERY: Patients undergo surgery.
ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines.
Patients also undergo computed tomography (CT) throughout the study and may undergo magnetic resonance imaging (MRI) and/or positron emission tomography (PET)/CT at screening.
After completion of study treatment, patients are followed up every 6 months for up to 10 years.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1100
-
Histologically or cytologically confirmed surgically resectable stage IIA to IIIB NSCLC according to the American Joint Committee on Cancer (AJCC) 9th edition (stage IIA to IIIB NSCLC up to single station N2, according to the AJCC 8th edition)
* Note: Patients with resectable stage N2a or T4 are eligible, but patients with stage N2b or N3 are not eligible. Patients with known EGFR or ALK alterations are excluded
-
Age ≥ 18 years
-
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (or Karnofsky ≥ 60%)
-
No prior systemic treatment for NSCLC within 5 years except stage 1 and 2 cancers treated with curative intent
-
No treatment for another malignancy within 3 years prior to registration, except for stage 1 or 2 cancers treated for curative intent; patients must be disease free for one year prior to registration. Patients with non-melanoma skin cancer, urothelial carcinoma in situ (Tis), noninvasive papillary carcinoma of the urinary bladder (Ta), prostatic intraepithelial neoplasia (PIN), ductal carcinoma in situ (DCIS) of the breast, or cervical intraepithelial neoplasia (CIN) of the uterine cervix are also eligible
-
No active autoimmune disease, interstitial lung disease, or transplant that precludes safe treatment with immune checkpoint inhibitors
-
HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 (surgery, adjuvant therapy) Surgical Procedure SURGERY: Patients undergo surgery within 28 days of registration. ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 1 (surgery, adjuvant therapy) Cisplatin SURGERY: Patients undergo surgery within 28 days of registration. ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 1 (surgery, adjuvant therapy) Carboplatin SURGERY: Patients undergo surgery within 28 days of registration. ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 1 (surgery, adjuvant therapy) Computed Tomography SURGERY: Patients undergo surgery within 28 days of registration. ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 1 (surgery, adjuvant therapy) Magnetic Resonance Imaging SURGERY: Patients undergo surgery within 28 days of registration. ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 1 (surgery, adjuvant therapy) Positron Emission Tomography SURGERY: Patients undergo surgery within 28 days of registration. ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy) Surgical Procedure NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines. SURGERY: Patients undergo surgery. ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy) Computed Tomography NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines. SURGERY: Patients undergo surgery. ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy) Magnetic Resonance Imaging NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines. SURGERY: Patients undergo surgery. ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy) Positron Emission Tomography NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines. SURGERY: Patients undergo surgery. ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 1 (surgery, adjuvant therapy) Gemcitabine SURGERY: Patients undergo surgery within 28 days of registration. ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 1 (surgery, adjuvant therapy) Docetaxel SURGERY: Patients undergo surgery within 28 days of registration. ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 1 (surgery, adjuvant therapy) Pemetrexed SURGERY: Patients undergo surgery within 28 days of registration. ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 1 (surgery, adjuvant therapy) Vinorelbine SURGERY: Patients undergo surgery within 28 days of registration. ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 1 (surgery, adjuvant therapy) Nivolumab SURGERY: Patients undergo surgery within 28 days of registration. ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 1 (surgery, adjuvant therapy) Pembrolizumab SURGERY: Patients undergo surgery within 28 days of registration. ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 1 (surgery, adjuvant therapy) Atezolizumab SURGERY: Patients undergo surgery within 28 days of registration. ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy) Cisplatin NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines. SURGERY: Patients undergo surgery. ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy) Carboplatin NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines. SURGERY: Patients undergo surgery. ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy) Gemcitabine NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines. SURGERY: Patients undergo surgery. ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy) Docetaxel NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines. SURGERY: Patients undergo surgery. ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy) Vinorelbine NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines. SURGERY: Patients undergo surgery. ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy) Pemetrexed NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines. SURGERY: Patients undergo surgery. ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy) Nivolumab NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines. SURGERY: Patients undergo surgery. ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy) Pembrolizumab NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines. SURGERY: Patients undergo surgery. ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening. Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy) Atezolizumab NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines. SURGERY: Patients undergo surgery. ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.
- Primary Outcome Measures
Name Time Method 3-year real-world event-free survival (rwEFS) From the date of randomization to the date of the first of the following events: failure to undergo resection for any reason, recurrence or progression at any time after surgery, or death from any cause, assessed at 3 years Time to event analyses will be summarized using the Kaplan-Meier method, where both the stratified and unstratified log-rank test will be used to compare the distributions across the treatment arms. For the primary analysis of 3-year rwEFS rate, we will compare the rwEFS curves at 3 years, using the difference in Kaplan-Meier estimates for the survival functions. The test statistic will be derived from the difference in the estimated Kaplan-Meier values between two arms at 3 years, using the Greenwood estimate of the variances. rwEFS rates at 1 year, 2 years, and 5 years will also be reported, along with 95% confidence intervals. The comparison of the rwEFS post 3-years between the two arms among patients who do not experience an event by 3 years, will involve assessing the probability of a longer rwEFS on the perioperative arm. Non-parametric estimation and inference methods will be used for analysis.
Overall survival (OS) From randomization until death from any cause, assessed up to 10 years Time to event analyses will be summarized using the Kaplan-Meier method, where both the stratified and unstratified log-rank test will be used to compare the distributions across the treatment arms. OS rates at 1 year, 2 years, and 5 years will also be reported, along with 95% confidence intervals.
- Secondary Outcome Measures
Name Time Method Rates of surgical resection Up to 10 years. Rates of resection will be tabulated and compared between the arms using chi-square tests or Fisher's exact tests. Univariable Cox models stratified by the stratification factors used in the randomization will be used to understand the impact of baseline covariates, resection status and systemic treatments on outcomes.
Rates of complete resection (R0) Up to 10 years. Rates of R0 resection will be tabulated and compared between the arms using chi-square tests or Fisher's exact tests. Univariable Cox models stratified by the stratification factors used in the randomization will be used to understand the impact of baseline covariates, resection status and systemic treatments on outcomes.
Incidence of adverse events (AEs) Up to 10 years. Adverse events will be recorded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 for each patient. Frequency tables and summary statistics will be used to determine the overall patterns within and across the arms.
Pathological complete response (pCR) Up to 10 years Pathologic complete response is defined as having no viable invasive cancer in the lung and lymph nodes (ypT0 ypN0 or ypT0/is ypN0) based on guidelines published by National Comprehensive Cancer Network and International Association for the Study of Lung Cancer. Cox regression models will be used to evaluate the association between pCR and rwEFS in perioperative arm (arm 2). The hazard ratio and corresponding 95% confidence interval will be reported. Multivariable landmark and time dependent models will be subsequently explored.
Trial Locations
- Locations (226)
South Sacramento Cancer Center
🇺🇸Sacramento, California, United States
Kaiser Permanente-San Francisco
🇺🇸San Francisco, California, United States
Kaiser Permanente-Santa Teresa-San Jose
🇺🇸San Jose, California, United States
Kaiser Permanente-Stockton
🇺🇸Stockton, California, United States
Kaiser Permanente-Vallejo
🇺🇸Vallejo, California, United States
Kaiser Permanente San Leandro
🇺🇸San Leandro, California, United States
Kaiser Permanente-Santa Rosa
🇺🇸Santa Rosa, California, United States
Kaiser San Rafael-Gallinas
🇺🇸San Rafael, California, United States
Medical Oncology Hematology Consultants PA
🇺🇸Newark, Delaware, United States
Cancer Care Center of O'Fallon
🇺🇸O'Fallon, Illinois, United States
HSHS Saint Elizabeth's Hospital
🇺🇸O'Fallon, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
Illinois CancerCare-Pekin
🇺🇸Pekin, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Illinois CancerCare-Peru
🇺🇸Peru, Illinois, United States
Valley Radiation Oncology
🇺🇸Peru, Illinois, United States
Illinois CancerCare-Princeton
🇺🇸Princeton, Illinois, United States
Memorial Hospital East
🇺🇸Shiloh, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Springfield Clinic
🇺🇸Springfield, Illinois, United States
Springfield Memorial Hospital
🇺🇸Springfield, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Illinois CancerCare - Washington
🇺🇸Washington, Illinois, United States
Rush-Copley Healthcare Center
🇺🇸Yorkville, Illinois, United States
Reid Health
🇺🇸Richmond, Indiana, United States
OSF Saint Anthony's Health Center
🇺🇸Alton, Illinois, United States
Rush - Copley Medical Center
🇺🇸Aurora, Illinois, United States
Illinois CancerCare-Bloomington
🇺🇸Bloomington, Illinois, United States
Illinois CancerCare-Canton
🇺🇸Canton, Illinois, United States
Memorial Hospital of Carbondale
🇺🇸Carbondale, Illinois, United States
SIH Cancer Institute
🇺🇸Carterville, Illinois, United States
Illinois CancerCare-Carthage
🇺🇸Carthage, Illinois, United States
Centralia Oncology Clinic
🇺🇸Centralia, Illinois, United States
Baptist Cancer Center-Grenada
🇺🇸Grenada, Mississippi, United States
Baptist Memorial Hospital and Cancer Center-Oxford
🇺🇸Oxford, Mississippi, United States
Central Care Cancer Center - Bolivar
🇺🇸Bolivar, Missouri, United States
Cox Cancer Center Branson
🇺🇸Branson, Missouri, United States
Mercy Cancer Center - Cape Girardeau
🇺🇸Cape Girardeau, Missouri, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
Siteman Cancer Center at West County Hospital
🇺🇸Creve Coeur, Missouri, United States
Parkland Health Center - Farmington
🇺🇸Farmington, Missouri, United States
Freeman Health System
🇺🇸Joplin, Missouri, United States
Mercy Hospital Joplin
🇺🇸Joplin, Missouri, United States
University Health Truman Medical Center
🇺🇸Kansas City, Missouri, United States
Lake Regional Hospital
🇺🇸Osage Beach, Missouri, United States
Mercy Clinic-Rolla-Cancer and Hematology
🇺🇸Rolla, Missouri, United States
Phelps Health Delbert Day Cancer Institute
🇺🇸Rolla, Missouri, United States
Heartland Regional Medical Center
🇺🇸Saint Joseph, Missouri, United States
Hi-Line Sletten Cancer Center
🇺🇸Havre, Montana, United States
Logan Health Medical Center
🇺🇸Kalispell, Montana, United States
Community Medical Center
🇺🇸Missoula, Montana, United States
The Valley Hospital - Luckow Pavilion
🇺🇸Paramus, New Jersey, United States
Neurosurgeons of New Jersey-Ridgewood
🇺🇸Ridgewood, New Jersey, United States
Valley Health System Ridgewood Campus
🇺🇸Ridgewood, New Jersey, United States
Valley Health System-Hematology/Oncology
🇺🇸Westwood, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Memorial Medical Center-Las Cruces
🇺🇸Las Cruces, New Mexico, United States
James J Peters VA Medical Center
🇺🇸Bronx, New York, United States
Glens Falls Hospital
🇺🇸Glens Falls, New York, United States
Upstate Cancer Center at Oswego
🇺🇸Oswego, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
SUNY Upstate Medical Center-Community Campus
🇺🇸Syracuse, New York, United States
Upstate Cancer Center at Verona
🇺🇸Verona, New York, United States
Wilmot Cancer Institute at Webster
🇺🇸Webster, New York, United States
Indu and Raj Soin Medical Center
🇺🇸Beavercreek, Ohio, United States
Saint Elizabeth Boardman Hospital
🇺🇸Boardman, Ohio, United States
Dayton Physicians LLC-Miami Valley South
🇺🇸Centerville, Ohio, United States
Oncology Hematology Care Inc-Kenwood
🇺🇸Cincinnati, Ohio, United States
Dayton Physician LLC - Englewood
🇺🇸Dayton, Ohio, United States
Armes Family Cancer Center
🇺🇸Findlay, Ohio, United States
Blanchard Valley Hospital
🇺🇸Findlay, Ohio, United States
Orion Cancer Care
🇺🇸Findlay, Ohio, United States
Dayton Physicians LLC-Atrium
🇺🇸Franklin, Ohio, United States
Dayton Physicians LLC-Wayne
🇺🇸Greenville, Ohio, United States
Wayne Hospital
🇺🇸Greenville, Ohio, United States
Greater Dayton Cancer Center
🇺🇸Kettering, Ohio, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
Dayton Physicians LLC - Troy
🇺🇸Troy, Ohio, United States
Saint Joseph Warren Hospital
🇺🇸Warren, Ohio, United States
Saint Elizabeth Youngstown Hospital
🇺🇸Youngstown, Ohio, United States
Cancer Centers of Southwest Oklahoma Research
🇺🇸Lawton, Oklahoma, United States
ThedaCare Regional Cancer Center
🇺🇸Appleton, Wisconsin, United States
ThedaCare Cancer Care - Berlin
🇺🇸Berlin, Wisconsin, United States
Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
Aspirus Medford Hospital
🇺🇸Medford, Wisconsin, United States
Zablocki Veterans Administration Medical Center
🇺🇸Milwaukee, Wisconsin, United States
ProHealth D N Greenwald Center
🇺🇸Mukwonago, Wisconsin, United States
ThedaCare Regional Medical Center - Neenah
🇺🇸Neenah, Wisconsin, United States
ThedaCare Cancer Care - New London
🇺🇸New London, Wisconsin, United States
ProHealth Oconomowoc Memorial Hospital
🇺🇸Oconomowoc, Wisconsin, United States
ThedaCare Cancer Care - Oshkosh
🇺🇸Oshkosh, Wisconsin, United States
Cancer Center of Western Wisconsin
🇺🇸New Richmond, Wisconsin, United States
Aspirus Cancer Care - James Beck Cancer Center
🇺🇸Rhinelander, Wisconsin, United States
ProHealth Waukesha Memorial Hospital
🇺🇸Waukesha, Wisconsin, United States
ThedaCare Cancer Care - Waupaca
🇺🇸Waupaca, Wisconsin, United States
Billings Clinic-Cody
🇺🇸Cody, Wyoming, United States
ThedaCare Cancer Care - Shawano
🇺🇸Shawano, Wisconsin, United States
UW Cancer Center at ProHealth Care
🇺🇸Waukesha, Wisconsin, United States
Aspirus Cancer Care - Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
Mercy Hospital Fort Smith
🇺🇸Fort Smith, Arkansas, United States
CARTI Cancer Center
🇺🇸Little Rock, Arkansas, United States
Kaiser Permanente-Deer Valley Medical Center
🇺🇸Antioch, California, United States
Kaiser Permanente Dublin
🇺🇸Dublin, California, United States
Kaiser Permanente-Fremont
🇺🇸Fremont, California, United States
Fresno Cancer Center
🇺🇸Fresno, California, United States
Kaiser Permanente-Fresno
🇺🇸Fresno, California, United States
Kaiser Permanente-Modesto
🇺🇸Modesto, California, United States
Kaiser Permanente Oakland-Broadway
🇺🇸Oakland, California, United States
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
Kaiser Permanente-Rancho Cordova Cancer Center
🇺🇸Rancho Cordova, California, United States
Kaiser Permanente- Marshall Medical Offices
🇺🇸Redwood City, California, United States
Kaiser Permanente-Richmond
🇺🇸Richmond, California, United States
Rohnert Park Cancer Center
🇺🇸Rohnert Park, California, United States
Kaiser Permanente-Roseville
🇺🇸Roseville, California, United States
The Permanente Medical Group-Roseville Radiation Oncology
🇺🇸Roseville, California, United States
Kaiser Permanente Downtown Commons
🇺🇸Sacramento, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Kaiser Permanente-South Sacramento
🇺🇸Sacramento, California, United States
Kaiser Permanente Medical Center - Santa Clara
🇺🇸Santa Clara, California, United States
Kaiser Permanente-Walnut Creek
🇺🇸Walnut Creek, California, United States
Beebe Medical Center
🇺🇸Lewes, Delaware, United States
Beebe South Coastal Health Campus
🇺🇸Millville, Delaware, United States
Kaiser Permanente Cancer Treatment Center
🇺🇸South San Francisco, California, United States
Kaiser Permanente-South San Francisco
🇺🇸South San Francisco, California, United States
Kaiser Permanente Medical Center-Vacaville
🇺🇸Vacaville, California, United States
Helen F Graham Cancer Center
🇺🇸Newark, Delaware, United States
Christiana Care Health System-Christiana Hospital
🇺🇸Newark, Delaware, United States
Beebe Health Campus
🇺🇸Rehoboth Beach, Delaware, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸Boise, Idaho, United States
Christiana Care Health System-Wilmington Hospital
🇺🇸Wilmington, Delaware, United States
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Kaiser Permanente Moanalua Medical Center
🇺🇸Honolulu, Hawaii, United States
Kootenai Health - Coeur d'Alene
🇺🇸Coeur d'Alene, Idaho, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Saint Alphonsus Cancer Care Center-Caldwell
🇺🇸Caldwell, Idaho, United States
Kootenai Clinic Cancer Services - Post Falls
🇺🇸Post Falls, Idaho, United States
Kootenai Clinic Cancer Services - Sandpoint
🇺🇸Sandpoint, Idaho, United States
Idaho Urologic Institute-Meridian
🇺🇸Meridian, Idaho, United States
Saint Alphonsus Cancer Care Center-Nampa
🇺🇸Nampa, Idaho, United States
Lakeview Hospital
🇺🇸Stillwater, Minnesota, United States
Minnesota Oncology Hematology PA-Woodbury
🇺🇸Woodbury, Minnesota, United States
Saint Louis Cancer and Breast Institute-Ballwin
🇺🇸Ballwin, Missouri, United States
Saint Mary's Hospital
🇺🇸Centralia, Illinois, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸Decatur, Illinois, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Illinois CancerCare-Dixon
🇺🇸Dixon, Illinois, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Illinois CancerCare-Eureka
🇺🇸Eureka, Illinois, United States
Illinois CancerCare-Galesburg
🇺🇸Galesburg, Illinois, United States
Illinois CancerCare-Kewanee Clinic
🇺🇸Kewanee, Illinois, United States
Illinois CancerCare-Macomb
🇺🇸Macomb, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
SSM Health Good Samaritan
🇺🇸Mount Vernon, Illinois, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Oncology Associates at Mercy Medical Center
🇺🇸Cedar Rapids, Iowa, United States
Central Care Cancer Center - Garden City
🇺🇸Garden City, Kansas, United States
Central Care Cancer Center - Great Bend
🇺🇸Great Bend, Kansas, United States
HaysMed
🇺🇸Hays, Kansas, United States
Lawrence Memorial Hospital
🇺🇸Lawrence, Kansas, United States
The University of Kansas Cancer Center - Olathe
🇺🇸Olathe, Kansas, United States
Salina Regional Health Center
🇺🇸Salina, Kansas, United States
University of Kansas Health System Saint Francis Campus
🇺🇸Topeka, Kansas, United States
King's Daughter's Medical Center
🇺🇸Ashland, Kentucky, United States
Owensboro Health Mitchell Memorial Cancer Center
🇺🇸Owensboro, Kentucky, United States
Christiana Care - Union Hospital
🇺🇸Elkton, Maryland, United States
Lahey Hospital and Medical Center
🇺🇸Burlington, Massachusetts, United States
Lahey Medical Center-Peabody
🇺🇸Peabody, Massachusetts, United States
Minnesota Oncology - Burnsville
🇺🇸Burnsville, Minnesota, United States
Cambridge Medical Center
🇺🇸Cambridge, Minnesota, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Fairview Clinics and Surgery Center Maple Grove
🇺🇸Maple Grove, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Saint John's Hospital - Healtheast
🇺🇸Maplewood, Minnesota, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Health Partners Inc
🇺🇸Minneapolis, Minnesota, United States
Monticello Cancer Center
🇺🇸Monticello, Minnesota, United States
New Ulm Medical Center
🇺🇸New Ulm, Minnesota, United States
Fairview Northland Medical Center
🇺🇸Princeton, Minnesota, United States
North Memorial Medical Health Center
🇺🇸Robbinsdale, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Saint Francis Regional Medical Center
🇺🇸Shakopee, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Rice Memorial Hospital
🇺🇸Willmar, Minnesota, United States
Baptist Memorial Hospital and Cancer Center-Desoto
🇺🇸Southhaven, Mississippi, United States
Fairview Lakes Medical Center
🇺🇸Wyoming, Minnesota, United States
Baptist Memorial Hospital and Cancer Center-Golden Triangle
🇺🇸Columbus, Mississippi, United States
Baptist Memorial Hospital and Cancer Center-Union County
🇺🇸New Albany, Mississippi, United States
Saint Louis Cancer and Breast Institute-South City
🇺🇸Saint Louis, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Veteran's Affairs Medical Center - Saint Louis
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital South
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center-South County
🇺🇸Saint Louis, Missouri, United States
Missouri Baptist Medical Center
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center at Christian Hospital
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center at Saint Peters Hospital
🇺🇸Saint Peters, Missouri, United States
Sainte Genevieve County Memorial Hospital
🇺🇸Sainte Genevieve, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
Missouri Baptist Sullivan Hospital
🇺🇸Sullivan, Missouri, United States
BJC Outpatient Center at Sunset Hills
🇺🇸Sunset Hills, Missouri, United States
Mercy Hospital Washington
🇺🇸Washington, Missouri, United States
Community Hospital of Anaconda
🇺🇸Anaconda, Montana, United States
Billings Clinic Cancer Center
🇺🇸Billings, Montana, United States
Bozeman Health Deaconess Hospital
🇺🇸Bozeman, Montana, United States
Benefis Sletten Cancer Institute
🇺🇸Great Falls, Montana, United States
Great Falls Clinic
🇺🇸Great Falls, Montana, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Mercy Hospital Oklahoma City
🇺🇸Oklahoma City, Oklahoma, United States
Saint Alphonsus Cancer Care Center-Baker City
🇺🇸Baker City, Oregon, United States
Saint Alphonsus Cancer Care Center-Ontario
🇺🇸Ontario, Oregon, United States
Christiana Care Health System-Concord Health Center
🇺🇸Chadds Ford, Pennsylvania, United States
McLeod Regional Medical Center
🇺🇸Florence, South Carolina, United States
Baptist Memorial Hospital and Cancer Center-Collierville
🇺🇸Collierville, Tennessee, United States
Langlade Hospital and Cancer Center
🇺🇸Antigo, Wisconsin, United States
Baptist Memorial Hospital and Cancer Center-Memphis
🇺🇸Memphis, Tennessee, United States
Aspirus Regional Cancer Center
🇺🇸Wausau, Wisconsin, United States
Aspirus Cancer Care - Wisconsin Rapids
🇺🇸Wisconsin Rapids, Wisconsin, United States