Testing the Addition of an Immunotherapy Drug, Atezolizumab, to the Usual Chemotherapy Treatment During Radiation Therapy for Superior Sulcus Non-small Cell Lung Cancer

NASSIST (Neoadjuvant Chemoradiation +/- Immunotherapy Before Surgery for Superior Sulcus Tumors): A Randomized Phase II Trial of Trimodality +/- Atezolizumab in Resectable Superior Sulcus Non-Small Cell Lung Cancer

This phase II trial tests the effect of atezolizumab given with usual chemotherapy during radiation therapy in treating patients with superior sulcus non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as cisplatin, carboplatin, etoposide, paclitaxel and pemetrexed, 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 beams to kill tumor cells and shrink tumors. Giving atezolizumab with usual chemotherapy and radiation therapy may lower the chance of the tumor from growing or spreading.

Study Overview

• Status: Withdrawn
• Conditions: Lung Non-Small Cell Carcinoma; Stage IIB Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Superior Sulcus Lung Carcinoma
• Intervention / Treatment: Drug: Carboplatin; Drug: Etoposide; Procedure: Magnetic Resonance Imaging; Drug: Cisplatin; Drug: Paclitaxel; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Therapeutic Conventional Surgery; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Drug: Pemetrexed; Biological: Atezolizumab; Radiation: External Beam Radiation Therapy

Detailed Description

PRIMARY OBJECTIVE:

I. To compare the pathologic complete response (pCR) by local review between participants randomized to conventional trimodality therapy, with or without atezolizumab.

SECONDARY OBJECTIVES:

I. To compare event-free survival (EFS) between the arms. II. To compare overall survival (OS) between the arms. III. To compare surgical resection rate and complete resection (R0) rate between the arms.

IV. To evaluate progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 among participants who do not undergo surgical resection, by treatment arm.

V. To compare the frequency and severity of toxicities between the arms.

ADDITIONAL OBJECTIVES:

I. To bank blood and tissue for future research. II. To evaluate the association between major pathologic response (MPR), as defined by the International Association for the Study of Lung Cancer (IASLC), and survival outcomes (OS, PFS).

III. To evaluate the association between pCR by centralized review and survival outcomes (OS, PFS).

IV. Evaluate the changes in fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) metrics (e.g., standardized uptake value [SUV] maximum [max], SUVpeak, SUVmax tumor-to-liver, SUVpeak tumor-to-liver, metabolic tumor volume, total lesion glycolysis, etc.) in participants randomized to receive trimodality therapy alone or in combination with atezolizumab and to evaluate the association with pCR.

V. Evaluate the extent to which the changes in diffusion weighted imaging (DWI)-magnetic resonance imagining (MRI) metrics (e.g., mean apparent diffusion coefficient or apparent diffusion coefficient [ADC] for the primary tumor, etc.) are associated with pCR in participants randomized to receive trimodality therapy alone or in combination with atezolizumab.

VI. Evaluate the extent to which changes in computed tomography (CT) tumor volume, unidimensional lesion changes per RECIST 1.1 and bidimensional lesion changes per World Health Organization (WHO) criteria are associated with pCR in participants randomized to receive trimodality therapy alone or in combination with atezolizumab.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1. Patients also receive one of the chemotherapy combinations below depending on their previous therapy and disease. Between the first day of chemotherapy and the first day of cycle 2 of chemotherapy, patients undergo external beam radiation therapy 5 days per week. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning 21 and 90 days after treatment, patients undergo surgery. Within 42 days after completion of surgery, patients then receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive one of the chemotherapy combinations below depending on their previous therapy and disease. Between the first day of chemotherapy and the first day of cycle 2 of chemotherapy, patients also undergo external beam radiation therapy 5 days per week. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning 21 and 90 days after treatment, patients undergo surgery.

Patients receive one of the chemotherapy combinations:

1. Cisplatin IV over 2 hours on day 1 and etoposide IV over 30-60 minutes on days 1-3.
2. Carboplatin IV over 60 minutes on day 1 and etoposide IV over 30-60 minutes on days 1-3.

3. Paclitaxel IV over 3 hours and carboplatin IV over 60 minutes on day 1.

   Patients with non-squamous NSCLC may receive one of the following combinations:

4. Pemetrexed IV over 10 minutes and carboplatin IV over 60 minutes on day 1.
5. Pemetrexed IV over 10 minutes and cisplatin IV over 2 hours on day 1.

Patients may undergo a PET scan, CT scan, and MRI on study. Patients also undergo tumor biopsies and blood sample collection throughout the trial.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
    • Caldwell, Idaho, United States, 83605
      • Saint Alphonsus Cancer Care Center-Caldwell
    • Coeur d'Alene, Idaho, United States, 83814
      • Kootenai Health - Coeur d'Alene
    • Nampa, Idaho, United States, 83687
      • Saint Alphonsus Cancer Care Center-Nampa
    • Post Falls, Idaho, United States, 83854
      • Kootenai Clinic Cancer Services - Post Falls
    • Sandpoint, Idaho, United States, 83864
      • Kootenai Cancer Clinic
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Rush - Copley Medical Center
    • Danville, Illinois, United States, 61832
      • Carle at The Riverfront
    • Effingham, Illinois, United States, 62401
      • Carle Physician Group-Effingham
    • Mattoon, Illinois, United States, 61938
      • Carle Physician Group-Mattoon/Charleston
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Iowa
    • Ames, Iowa, United States, 50010
      • Mary Greeley Medical Center
    • Ames, Iowa, United States, 50010
      • McFarland Clinic - Ames
    • Boone, Iowa, United States, 50036
      • McFarland Clinic - Boone
    • Fort Dodge, Iowa, United States, 50501
      • McFarland Clinic - Trinity Cancer Center
    • Jefferson, Iowa, United States, 50129
      • McFarland Clinic - Jefferson
    • Marshalltown, Iowa, United States, 50158
      • McFarland Clinic - Marshalltown
  • Mississippi
    • Columbus, Mississippi, United States, 39705
      • Baptist Memorial Hospital and Cancer Center-Golden Triangle
    • Grenada, Mississippi, United States, 38901
      • Baptist Cancer Center-Grenada
    • New Albany, Mississippi, United States, 38652
      • Baptist Memorial Hospital and Cancer Center-Union County
    • Oxford, Mississippi, United States, 38655
      • Baptist Memorial Hospital and Cancer Center-Oxford
    • Southhaven, Mississippi, United States, 38671
      • Baptist Memorial Hospital and Cancer Center-Desoto
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Missoula, Montana, United States, 59804
      • Community Medical Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
    • New York, New York, United States, 10011
      • Mount Sinai Chelsea
  • Ohio
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Cancer Center-UC Medical Center
    • Columbus, Ohio, United States, 43219
      • The Mark H Zangmeister Center
    • West Chester, Ohio, United States, 45069
      • University of Cincinnati Cancer Center-West Chester
    • Westerville, Ohio, United States, 43081
      • Saint Ann's Hospital
    • Zanesville, Ohio, United States, 43701
      • Genesis Healthcare System Cancer Care Center
  • Oklahoma
    • Lawton, Oklahoma, United States, 73505
      • Cancer Centers of Southwest Oklahoma Research
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Ontario, Oregon, United States, 97914
      • Saint Alphonsus Medical Center-Ontario
  • Tennessee
    • Collierville, Tennessee, United States, 38017
      • Baptist Memorial Hospital and Cancer Center-Collierville
    • Memphis, Tennessee, United States, 38120
      • Baptist Memorial Hospital and Cancer Center-Memphis
  • Vermont
    • Saint Johnsbury, Vermont, United States, 05819
      • Norris Cotton Cancer Center-North
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Clinic-Minocqua Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• STEP 1 RANDOMIZATION: Participants must have histologically confirmed cT3/T4, N0/1, M0 non-small cell lung cancer (NSCLC) of the superior sulcus arising in the apex of the lung, involving apical chest wall structures (parietal pleura and beyond) above the level of the second rib
• STEP 1 RANDOMIZATION: Participants must have eligibility affirmed by a thoracic surgeon, medical oncologist and radiation oncologist. Participant must be a candidate for surgical resection and chemoradiation therapy. The site treating investigator must sign off to indicate that eligibility has been affirmed by each specialist
• STEP 1 RANDOMIZATION: Participants may have measurable or non-measurable disease. Measurable disease must be assessed within 28 days prior to Step 1 Randomization. Non-measurable disease must be assessed within 42 days prior to Step 1 Randomization. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form
• STEP 1 RANDOMIZATION: Participants must have an MRI or CT scan of the brain (with contrast highly recommend) within 42 days prior to Step 1 Randomization

• STEP 1 RANDOMIZATION: Participants must have a CT (chest with contrast highly recommended), contrast MRI (thoracic inlet), and FDG-PET/CT performed within 28 days prior to Step 1 Randomization

  • Note: DWI (Diffusion weighting imaging) is highly recommended on the MRI
• STEP 1 RANDOMIZATION: Participants may participate in concomitant non-therapeutic trials (e.g., palliative care assessment or quality of life studies)
• STEP 1 RANDOMIZATION: History and physical exam must be obtained within 28 days of Step 1 Randomization
• STEP 1 RANDOMIZATION: Participants must have Zubrod performance status of 0-1 documented within 28 days prior to Step 1 Randomization
• STEP 1 RANDOMIZATION: Participants must be >= 18 years old
• STEP 1 RANDOMIZATION: Leukocytes >= 3,000/uL (within 28 days prior to Step 1 Randomization)
• STEP 1 RANDOMIZATION: Absolute neutrophil count >= 1,500/uL (within 28 days prior to Step 1 Randomization)
• STEP 1 RANDOMIZATION: Platelets >= 100,000/uL (within 28 days prior to Step 1 Randomization)
• STEP 1 RANDOMIZATION: Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to Step 1 Randomization)
• STEP 1 RANDOMIZATION: Participants with known Gilbert disease: total bilirubin =< 3 x (ULN) (within 28 days prior to Step 1 Randomization)
• STEP 1 RANDOMIZATION: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x institutional ULN (within 28 days prior to Step 1 Randomization)
• STEP 1 RANDOMIZATION: Hemoglobin >= 9 g/dL (within 28 days prior to Step 1 Randomization)
• STEP 1 RANDOMIZATION: Participants must not have higher than grade 2 hypercalcemia prior to Step I Randomization
• STEP 1 RANDOMIZATION: Participants must have a serum creatinine =< the institutional upper limit of normal (IULN) OR measured OR calculated creatinine clearance >= 50 mL/min using the following Cockcroft-Gault formula. This specimen must have been drawn and processed within 28 days prior to Step 1 Randomization
• STEP 1 RANDOMIZATION: Participants with known human immunodeficiency virus (HIV)-infection must be receiving anti-retroviral therapy and have undetectable viral load test within 6 months prior to Step 1 Randomization
• STEP 1 RANDOMIZATION: Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within 28 days prior to Step 1 Randomization
• STEP 1 RANDOMIZATION: Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load within in 28 days prior to Step 1 Randomization
• STEP 1 RANDOMIZATION: Participants of reproductive potential must have a negative serum pregnancy test within 14 days prior to Step 1 Randomization
• STEP 1 RANDOMIZATION: Participants must be offered the opportunity to participate in specimen banking
• STEP 1 RANDOMIZATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines. For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
• STEP 2 SURGERY: Participants must have a CT scan of the chest with contrast, FDG-PET/CT scan and MRI scan of the thoracic inlet (with intravenous contrast and DWI highly recommended) within 28 days prior to Step 2 Registration
• STEP 2 SURGERY: Participants must be evaluated for appropriateness of surgery by a thoracic surgeon within 6 weeks after completion of neoadjuvant therapy prior to Step 2 Registration
• STEP 2 SURGERY: Participant's surgery must occur between 21 and 90 days following the end of participant's final cycle of chemotherapy +/- atezolizumab
• STEP 2 SURGERY: Participants must have received at least two cycles of all assigned protocol drugs during neoadjuvant protocol treatment and must have received at least 45 GY RT of the planned 61.2 GY RT during neoadjuvant protocol treatment
• STEP 2 SURGERY: Participants must have a Zubrod Performance Status of 0-1 documented within 28 days prior to Step 2 Registration
• STEP 2 SURGERY: Participants must have postoperative predicted forced expiratory volume in 1 second (FEV1) > 35% and postoperative predicted diffusion capacity of the lung for carbon monoxide (DLCO) > 35%. Pulmonary function tests to ascertain these values must be obtained within 28 days prior to Step 2 Registration
• STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): Participants must have received surgical resection of the lung cancer and side effects must have recovered to =< grade 2 within 42 days after surgery and prior to Step 3 Registration
• STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): Participants must have a Zubrod Performance Status of 0-1 documented within 28 days prior to Step 3 Registration
• STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): Leukocytes >= 3,000/uL (within 28 days prior to Step 3 Registration)
• STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): Absolute neutrophil count >= 1,000/uL (within 28 days prior to Step 3 Registration)
• STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): Platelets >= 100,000/uL (within 28 days prior to Step 3 Registration)
• STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): Hemoglobin >= 9 g/dL (within 28 days prior to Step 3 Registration)
• STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): Total bilirubin =< institutional upper limit of normal (ULN) (within 28 days prior to Step 3 Registration)
• STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): AST and ALT =< 3 x institutional ULN (within 28 days prior to Step 3 Registration)
• STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): Participants must have adequate kidney function defined as creatinine =< 1.5 x ULN documented within 28 days prior to Step 3 Registration

Exclusion Criteria:

• STEP 1 RANDOMIZATION: Participants must not have had prior therapy for this cancer including surgery, chemotherapy, immunotherapy, targeted therapy agent, and/or radiation therapy
• STEP 1 RANDOMIZATION: Participants must not have undergone prior radiation to overlapping regions of planned protocol radiation therapy (RT) treatment area
• STEP 1 RANDOMIZATION: Participants must not have had prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• STEP 1 RANDOMIZATION: Participants must not have had prior treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks prior to Step 1 Randomization
• STEP 1 RANDOMIZATION: Participants must not have a known allergy or hypersensitivity to any component of the carboplatin, pemetrexed, cisplatin, etoposide and paclitaxel formulation
• STEP 1 RANDOMIZATION: Participants must not have any grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., participants with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, and myocardial infarction within 3 months, or serious uncontrolled cardiac arrhythmia
• STEP 1 RANDOMIZATION: Participants must not have known active tuberculosis (TB)
• STEP 1 RANDOMIZATION: Participants must not have uncontrolled non-malignant pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (more than once a month). Note: Participants with indwelling catheters (e.g., PleurX [registered trademark]) are allowed
• STEP 1 RANDOMIZATION: Patients must not have undergone prior allogeneic stem cell transplantation or prior solid organ transplantation
• STEP 1 RANDOMIZATION: Participants must NOT have a history of severe allergic, anaphylactic, or other known hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• STEP 1 RANDOMIZATION: Participants must NOT have a known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
• STEP 1 RANDOMIZATION: Participants must not have severe or active infections within 28 days prior to Step 1 Randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• STEP 1 RANDOMIZATION: Participants must not have active autoimmune disease requiring therapy within the past 6 months. Participants must not have active autoimmune disease that has required systemic treatment within the past two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Autoimmune diseases include, but are not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis. This protocol includes an immunotherapy agent which can precipitate known autoimmune diseases
• STEP 1 RANDOMIZATION: Participants must not have history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (e.g., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis. This protocol includes an immunotherapy agent which can precipitate known pneumonitis
• STEP 1 RANDOMIZATION: Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
• STEP 1 RANDOMIZATION: Participants must not have received a live attenuated vaccination within 28 days prior to Step 1 Randomization. All coronavirus disease 2019 (COVID-19) vaccines that have received Food and Drug Administration (FDA) approval or FDA emergency use authorization are acceptable
• STEP 1 RANDOMIZATION: Participants must not have had a major surgery within 14 days prior to Step 1 Randomization. Participants must have fully recovered from the effects of prior surgery in the opinion of the treating investigator
• STEP 1 RANDOMIZATION: Participants must not be pregnant or nursing due to carcinogenic and teratogenic effects of treatment. Women/men of reproductive potential must have agreed to use an effective contraceptive method while on study treatment and for 5 months after the last dose. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined, he/she is responsible for beginning contraceptive measures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (atezolizumab, chemotherapy, RT, surgery); Patients receive atezolizumab IV over 30-60 minutes on day 1. Patients also receive one of the chemotherapy combinations below depending on their previous therapy and disease. Between the first day of chemotherapy and the first day of cycle 2 of chemotherapy, patients undergo external beam radiation therapy 5 days per week. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning 21 and 90 days after treatment, patients undergo surgery. Within 42 days after completion of surgery, patients then receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients may undergo a PET scan, CT scan, and MRI on study. Patients also undergo tumor biopsies and blood sample collection throughout the trial.	Drug: Carboplatin; Given IV; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carboplatinum; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; JM8; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; VP 16213; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic resonance imaging (procedure); Drug: Cisplatin; Given IV; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Procedure: Biopsy; Undergo tumor biopsy; Other Names: Bx; BIOPSY_TYPE; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Therapeutic Conventional Surgery; Undergo surgery; Procedure: Computed Tomography; Undergo PET/CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Procedure: Positron Emission Tomography; Undergo PET/CT scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Drug: Pemetrexed; Given IV; Other Names: MTA; Multitargeted Antifolate; Pemfexy; Biological: Atezolizumab; Given IV; Other Names: Tecentriq; MPDL3280A; RO5541267; RG7446; MPDL 3280A; MPDL 328OA; MPDL-3280A; MPDL328OA; Radiation: External Beam Radiation Therapy; Undergo external beam radiation therapy; Other Names: EBRT; Definitive Radiation Therapy; External Beam Radiation; External Beam Radiotherapy; External Beam RT; external radiation; External Radiation Therapy; external-beam radiation; Radiation, External Beam; Teleradiotherapy; Teletherapy; Teletherapy Radiation; External Beam Radiotherapy (conventional)
Active Comparator: Arm II (chemotherapy, RT, surgery); Patients receive one of the chemotherapy combinations below depending on their previous therapy and disease. Between the first day of chemotherapy and the first day of cycle 2 of chemotherapy, patients also undergo external beam radiation therapy 5 days per week. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning 21 and 90 days after treatment, patients undergo surgery. Patients may undergo a PET scan, CT scan, and MRI on study. Patients also undergo tumor biopsies and blood sample collection throughout the trial.	Drug: Carboplatin; Given IV; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carboplatinum; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; JM8; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; VP 16213; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic resonance imaging (procedure); Drug: Cisplatin; Given IV; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Procedure: Biopsy; Undergo tumor biopsy; Other Names: Bx; BIOPSY_TYPE; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Therapeutic Conventional Surgery; Undergo surgery; Procedure: Computed Tomography; Undergo PET/CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Procedure: Positron Emission Tomography; Undergo PET/CT scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Drug: Pemetrexed; Given IV; Other Names: MTA; Multitargeted Antifolate; Pemfexy; Radiation: External Beam Radiation Therapy; Undergo external beam radiation therapy; Other Names: EBRT; Definitive Radiation Therapy; External Beam Radiation; External Beam Radiotherapy; External Beam RT; external radiation; External Radiation Therapy; external-beam radiation; Radiation, External Beam; Teleradiotherapy; Teletherapy; Teletherapy Radiation; External Beam Radiotherapy (conventional)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pathologic complete response (pCR) by local review	Up to 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS)	Defined as From date of Step1 Randomization to date of first documentation of progression that renders participant unable to receive planned protocol surgery, off protocol therapy for any reason without subsequent protocol surgery, relapse after surgery, symptomatic deterioration or death due to any reason, whichever comes first. The primary analysis of EFS will be done using a 1-sided 15% level log-rank test. Will be estimated using the method of Kaplan-Meier. 95% confidence intervals for the medians will be constructed using the method of Brookmeyer-Crowley. Fine-Gray method will be used for a competing risk analysis.	Up to 6 years
Overall survival (OS)	Will be estimated using the method of Kaplan-Meier. 95% confidence intervals for the medians will be constructed using the method of Brookmeyer-Crowley.	From date of Step 1 Randomization to date of death due to any cause, assessed up to 6 years
Surgical resection rate		Up to 6 years
Complete resection (R0) rate		Up to 6 years
Progression-free survival (PFS)	Will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be estimated using the method of Kaplan-Meier. 95% confidence intervals for the medians will be constructed using the method of Brookmeyer-Crowley.	From date of Step 1 Randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause, whichever comes first, assessed up to 6 years
Incidence of adverse events	Will compare the frequency and severity of toxicities between the arms.	Up to 6 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bank blood and tissue for future research		Up to 6 years
Major pathologic response	Defined by the International Association for the Study of Lung Cancer, will be associated with and survival outcomes (OS, PFS).	Up to 6 years
pCR by centralized review	Will be associated with survival outcomes (OS, PFS).	Up to 6 years
Changes in fludeoxyglucose F-18-positron emission tomography metrics		Baseline up to 6 years
Changes in diffusion weighted imaging (DWI)-magnetic resonance imagining (MRI) metrics	Changes in DWI-MRI metrics will be associated with pCR between arms.	Baseline up to 6 years
Changes in computed tomography tumor volume	Will assess unidimensional lesion changes per RECIST 1.1 and bidimensional lesion changes per World Health Organization (WHO) criteria. Will be associated with pCR in participants randomized to receive trimodality therapy alone or in combination with atezolizumab.	Baseline up to 6 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Raymond U Osarogiagbon, SWOG Cancer Research Network

Study record dates

Study Major Dates

• Study Start (Estimated): September 9, 2021
• Primary Completion (Estimated): May 10, 2031
• Study Completion (Estimated): May 10, 2031

Study Registration Dates

• First Submitted: August 3, 2021
• First Submitted That Met QC Criteria: August 3, 2021
• First Posted (Actual): August 4, 2021

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Dermatologic Agents; Immune Checkpoint Inhibitors; Keratolytic Agents; Folic Acid Antagonists; Carboplatin; Etoposide; Etoposide phosphate; Paclitaxel; Cisplatin; Podophyllotoxin; Albumin-Bound Paclitaxel; Antibodies, Monoclonal; Pemetrexed; Atezolizumab
• Other Study ID Numbers: NCI-2021-08318 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180888 (U.S. NIH Grant/Contract); S1934 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: "NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No