Atezolizumab, Pemetrexed Disodium, Cisplatin, and Surgery With or Without Radiation Therapy in Treating Patients With Stage I-III Pleural Malignant Mesothelioma

A Feasibility Trial of Neoadjuvant Cisplatin-Pemetrexed With Atezolizumab in Combination and in Maintenance for Resectable Malignant Pleural Mesothelioma

This phase I pilot trial studies how well atezolizumab, pemetrexed disodium, cisplatin, and surgery with or without radiation therapy works in treating patients with stage I-III pleural malignant mesothelioma. 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. Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, 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. Giving atezolizumab, pemetrexed disodium, and cisplatin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving atezolizumab after surgery may kill any remaining tumor cells.

Study Overview

• Status: Active, not recruiting
• Conditions: Biphasic Mesothelioma; Epithelioid Mesothelioma; Stage III Pleural Malignant Mesothelioma AJCC v7; Stage I Pleural Malignant Mesothelioma AJCC v7; Stage IA Pleural Malignant Mesothelioma AJCC v7; Stage IB Pleural Malignant Mesothelioma AJCC v7; Stage II Pleural Malignant Mesothelioma AJCC v7
• Intervention / Treatment: Radiation: Radiation Therapy; Drug: Cisplatin; Drug: Pemetrexed Disodium; Drug: Atezolizumab; Procedure: Extrapleural Pneumonectomy; Procedure: Pleurectomy

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate if the regimen of neoadjuvant cisplatin-pemetrexed disodium (pemetrexed)-atezolizumab, surgery +/- radiation, then maintenance atezolizumab is feasible and safe for patients with resectable malignant pleural mesothelioma.

SECONDARY OBJECTIVES:

I. To evaluate progression free survival (both by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 and also using a modified RECIST for pleural tumors) in patients with resectable malignant pleural mesothelioma treated with a regimen of neoadjuvant cisplatin-pemetrexed-atezolizumab, surgery +/- radiation, followed by one year of maintenance atezolizumab.

II. To evaluate overall survival in patients with resectable malignant pleural mesothelioma treated with a regimen of neoadjuvant cisplatin-pemetrexed-atezolizumab, surgery +/- radiation, followed by one year of maintenance atezolizumab.

III. To evaluate response rate (confirmed and unconfirmed, complete and partial, both by RECIST 1.1 and also using a modified RECIST for pleural tumors) in the subset of this patient population with measurable disease.

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To evaluate the association between immunohistochemical (IHC) expression of PD-L1 in tumors and clinical outcomes in mesothelioma patients treated with trimodality/bimodality therapy including atezolizumab (anti-PD-L1).

II. To evaluate the association between expression of immune-related genes identified by Immune Nanostring (depending on ribonucleic acid [RNA] availability) and clinical outcomes in mesothelioma patients treated with trimodality/bimodality therapy including atezolizumab.

III. To evaluate the association between multiplex immunofluorescence (IF) of up to 10 immune markers in two panels and clinical outcomes in mesothelioma patients treated with trimodality/bimodality therapy including atezolizumab.

OUTLINE:

NEOADJUVANT: Patients receive atezolizumab intravenously (IV) over 30-60 minutes, pemetrexed disodium IV over 10 minutes, and cisplatin IV over 2 hours on day 1. Cycles repeats every 21 days for 4 cycles in the absence of disease progression or unexpected toxicity.

SURGERY: Within 21-90 days after completion of neoadjuvant therapy, patients undergo extrapleural pneumonectomy (EPP) or pleurectomy/decortication (PD). Patients who undergo EPP will then undergo radiation therapy (RT).

MAINTENANCE: Within 90 days after completion of either PD or radiation (post-EPP), patients receive atezolizumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 1 year in the absence of disease progression or unexpected toxicity.

After completion of study treatment, patients are followed up for up to 3 years.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital in Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • CHI Saint Vincent Cancer Center Hot Springs
  • California
    • Arroyo Grande, California, United States, 93420
      • PCR Oncology
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Colorado Springs, Colorado, United States, 80907
      • Rocky Mountain Cancer Centers-Penrose
    • Denver, Colorado, United States, 80210
      • Porter Adventist Hospital
    • Durango, Colorado, United States, 81301
      • Mercy Medical Center
    • Durango, Colorado, United States, 81301
      • Southwest Oncology PC
    • Golden, Colorado, United States, 80401
      • Mountain Blue Cancer Care Center
    • Lakewood, Colorado, United States, 80228
      • Saint Anthony Hospital
    • Lakewood, Colorado, United States, 80228
      • Rocky Mountain Cancer Centers-Lakewood
    • Littleton, Colorado, United States, 80122
      • Littleton Adventist Hospital
    • Longmont, Colorado, United States, 80501
      • Longmont United Hospital
    • Longmont, Colorado, United States, 80501
      • Rocky Mountain Cancer Centers-Longmont
    • Parker, Colorado, United States, 80138
      • Parker Adventist Hospital
    • Parker, Colorado, United States, 80138
      • Rocky Mountain Cancer Centers-Parker
    • Pueblo, Colorado, United States, 81004
      • Saint Mary Corwin Medical Center
    • Pueblo, Colorado, United States, 81008
      • Rocky Mountain Cancer Centers - Pueblo
    • Thornton, Colorado, United States, 80260
      • Rocky Mountain Cancer Centers-Thornton
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson 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
    • Meridian, Idaho, United States, 83642
      • Idaho Urologic Institute-Meridian
    • 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
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Carbondale, Illinois, United States, 62902
      • Memorial Hospital of Carbondale
    • Carterville, Illinois, United States, 62918
      • SIH Cancer Institute
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Centralia, Illinois, United States, 62801
      • Centralia Oncology Clinic
    • Danville, Illinois, United States, 61832
      • Carle at The Riverfront
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Illinois - Decatur
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Effingham, Illinois, United States, 62401
      • Carle Physician Group-Effingham
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Galesburg, Illinois, United States, 61401
      • Western Illinois Cancer Treatment Center
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Mattoon, Illinois, United States, 61938
      • Carle Physician Group-Mattoon/Charleston
    • O'Fallon, Illinois, United States, 62269
      • Cancer Care Center of O'Fallon
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Pekin, Illinois, United States, 61554
      • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peoria, Illinois, United States, 61615
      • OSF Saint Francis Radiation Oncology at Peoria Cancer Center
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Peru, Illinois, United States, 61354
      • Valley Radiation Oncology
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare-Princeton
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
    • Springfield, Illinois, United States, 62702
      • Springfield Clinic
    • Swansea, Illinois, United States, 62226
      • Southwest Illinois Health Services LLP
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Urbana, Illinois, United States, 61801
      • The Carle Foundation Hospital
    • Yorkville, Illinois, United States, 60560
      • Rush-Copley Healthcare 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
    • Clive, Iowa, United States, 50325
      • Mercy Cancer Center-West Lakes
    • Clive, Iowa, United States, 50325
      • Medical Oncology and Hematology Associates-West Des Moines
    • Council Bluffs, Iowa, United States, 51503
      • Alegent Health Mercy Hospital
    • Creston, Iowa, United States, 50801
      • Greater Regional Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50314
      • Mission Cancer and Blood - Laurel
    • 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
    • West Des Moines, Iowa, United States, 50266
      • Mercy Medical Center-West Lakes
  • Kansas
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Hospitals Wichita
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Flaget Memorial Hospital
    • Corbin, Kentucky, United States, 40701
      • Commonwealth Cancer Center-Corbin
    • Lexington, Kentucky, United States, 40504
      • Saint Joseph Radiation Oncology Resource Center
    • Lexington, Kentucky, United States, 40509
      • Saint Joseph Hospital East
    • London, Kentucky, United States, 40741
      • Saint Joseph London
    • Louisville, Kentucky, United States, 40202
      • Jewish Hospital
    • Louisville, Kentucky, United States, 40245
      • UofL Health Medical Center Northeast
    • Louisville, Kentucky, United States, 40215
      • Saints Mary and Elizabeth Hospital
    • Shepherdsville, Kentucky, United States, 40165
      • Jewish Hospital Medical Center South
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center Jefferson
  • Michigan
    • Brownstown, Michigan, United States, 48183
      • Henry Ford Cancer Institute-Downriver
    • Clinton Township, Michigan, United States, 48038
      • Henry Ford Macomb Hospital-Clinton Township
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Shelby, Michigan, United States, 48315
      • Henry Ford Macomb Health Center - Shelby Township
    • West Bloomfield, Michigan, United States, 48322
      • Henry Ford West Bloomfield Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
  • Missouri
    • Bonne Terre, Missouri, United States, 63628
      • Parkland Health Center-Bonne Terre
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63703
      • Southeast Cancer Center
    • Jefferson City, Missouri, United States, 65109
      • Capital Region Southwest Campus
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Sainte Genevieve, Missouri, United States, 63670
      • Sainte Genevieve County Memorial Hospital
    • Sullivan, Missouri, United States, 63080
      • Missouri Baptist Sullivan Hospital
    • Sunset Hills, Missouri, United States, 63127
      • BJC Outpatient Center at Sunset Hills
  • Montana
    • Anaconda, Montana, United States, 59711
      • Community Hospital of Anaconda
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Helena, Montana, United States, 59601
      • Saint Peter's Community Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Missoula, Montana, United States, 59804
      • Community Medical Hospital
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • CHI Health Saint Francis
    • Kearney, Nebraska, United States, 68847
      • CHI Health Good Samaritan
    • Kearney, Nebraska, United States, 68845
      • Heartland Hematology and Oncology
    • Lincoln, Nebraska, United States, 68510
      • Saint Elizabeth Regional Medical Center
    • Omaha, Nebraska, United States, 68124
      • Alegent Health Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68122
      • Alegent Health Immanuel Medical Center
    • Omaha, Nebraska, United States, 68130
      • Alegent Health Lakeside Hospital
    • Omaha, Nebraska, United States, 68131
      • Creighton University Medical Center
    • Omaha, Nebraska, United States, 68122
      • Hematology and Oncology Consultants PC
    • Papillion, Nebraska, United States, 68046
      • Midlands Community Hospital
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Comprehensive Cancer Centers of Nevada - Henderson
    • Henderson, Nevada, United States, 89052
      • OptumCare Cancer Care at Seven Hills
    • Las Vegas, Nevada, United States, 89102
      • OptumCare Cancer Care at Charleston
    • Las Vegas, Nevada, United States, 89106
      • Radiation Oncology Centers of Nevada Central
    • Las Vegas, Nevada, United States, 89109
      • GenesisCare USA - Las Vegas
    • Las Vegas, Nevada, United States, 89119
      • Radiation Oncology Centers of Nevada Southeast
    • Las Vegas, Nevada, United States, 89128
      • Comprehensive Cancer Centers of Nevada - Northwest
    • Las Vegas, Nevada, United States, 89128
      • OptumCare Cancer Care at MountainView
    • Las Vegas, Nevada, United States, 89135
      • Alliance for Childhood Diseases/Cure 4 the Kids Foundation
    • Las Vegas, Nevada, United States, 89144
      • Comprehensive Cancer Centers of Nevada-Summerlin
    • Las Vegas, Nevada, United States, 89148
      • Comprehensive Cancer Centers of Nevada
    • Las Vegas, Nevada, United States, 89148
      • OptumCare Cancer Care at Fort Apache
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada - Central Valley
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
    • Reno, Nevada, United States, 89503
      • Saint Mary's Regional Medical Center
    • Reno, Nevada, United States, 89509
      • Radiation Oncology Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • Good Samaritan Hospital - Cincinnati
    • Cincinnati, Ohio, United States, 45242
      • Bethesda North Hospital
    • Cincinnati, Ohio, United States, 45247
      • TriHealth Cancer Institute-Westside
    • Cincinnati, Ohio, United States, 45255
      • TriHealth Cancer Institute-Anderson
  • Oklahoma
    • Lawton, Oklahoma, United States, 73505
      • Cancer Centers of Southwest Oklahoma Research
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute (UPCI)
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Memorial Hospital
    • Hixson, Tennessee, United States, 37343
      • Pulmonary Medicine Center of Chattanooga-Hixson
    • Ooltewah, Tennessee, United States, 37363
      • Memorial GYN Plus
  • Texas
    • Bryan, Texas, United States, 77802
      • Saint Joseph Regional Cancer Center
    • Conroe, Texas, United States, 77384
      • MD Anderson in The Woodlands
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • Houston, Texas, United States, 77026-1967
      • Lyndon Baines Johnson General Hospital
    • Houston, Texas, United States, 77079
      • MD Anderson West Houston
    • League City, Texas, United States, 77573
      • MD Anderson League City
    • Richardson, Texas, United States, 75080
      • UT Southwestern Clinical Center at Richardson/Plano
    • Sugar Land, Texas, United States, 77478
      • MD Anderson in Sugar Land
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center
  • Washington
    • Bellevue, Washington, United States, 98004
      • Overlake Medical Center
    • Bremerton, Washington, United States, 98310
      • Harrison HealthPartners Hematology and Oncology-Bremerton
    • Bremerton, Washington, United States, 98310
      • Harrison Medical Center
    • Burien, Washington, United States, 98166
      • Highline Medical Center-Main Campus
    • Enumclaw, Washington, United States, 98022
      • Saint Elizabeth Hospital
    • Federal Way, Washington, United States, 98003
      • Saint Francis Hospital
    • Lakewood, Washington, United States, 98499
      • Saint Clare Hospital
    • Poulsbo, Washington, United States, 98370
      • Harrison HealthPartners Hematology and Oncology-Poulsbo
    • Renton, Washington, United States, 98055
      • Valley Medical Center
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center - Montlake
    • Seattle, Washington, United States, 98109
      • FHCC South Lake Union
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties PLLC
    • Tacoma, Washington, United States, 98405
      • Franciscan Research Center-Northwest Medical Plaza
  • Wyoming
    • Cody, Wyoming, United States, 82414
      • Billings Clinic-Cody
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer 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: NEOADJUVANT
• Patient must have stage I-III malignant pleural mesothelioma that is deemed resectable and must be planning to undergo pleurectomy decortication (P/D) or extrapleural pneumonectomy (EPP)
• Patient must have epithelioid or biphasic histology (sarcomatoid histology is excluded); histologic diagnosis and typing of mesothelioma requires at least a core needle biopsy or surgical biopsy of the pleura via thoracoscopy and small thoracotomy; cytology only will not be regarded as sufficient for the diagnosis
• Patient must have computed tomography (CT) chest/abdomen/pelvis with contrast or fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/CT scan performed within 28 days prior to step 1 registration
• Patients must have non-measurable or measurable disease documented by CT or magnetic resonance imaging (MRI); the CT from a combined PET/CT may be used to document only non-measurable disease unless it is of diagnostic quality; measurable disease must be assessed within 28 days prior to step 1 registration; non-measurable disease must be assessed within 42 days prior to step 1 registration; all disease must be assessed and documented on the RECIST 1.1 and modified RECIST baseline tumor assessment form
• Patient must have undergone extended surgical staging including mediastinoscopy or endobronchial ultrasound; at minimum, samples must be obtained from the mediastinal stations 4R, 7 (subcarinal), and 4L; this surgical staging must be performed within 42 days prior to step 1 registration; patient must be T1-3 and N0-N2 (single station)
• Patient must undergo video-assisted thoracoscopic surgery and diagnostic laparoscopy within 28 days prior to step 1 registration to rule out peritoneal disease spread
• Patient must have consultation with a surgeon within 21 days prior to step 1 registration; the surgeon must confirm that the patient's disease is resectable by pleurectomy decortication (P/D) or extrapleural pneumonectomy (EPP) and that the patient is an appropriate candidate for the surgical procedures
• Patient must not have had prior immunotherapy or chemotherapy for malignant pleural mesothelioma
• Patient must have Zubrod performance status 0 or 1 documented within 28 days prior to step 1 registration
• Patients requiring hearing aids or reporting hearing loss must have audiogram performed within 28 days prior to step 1 registration
• Patient must have not had any major surgery or radiation within 28 days prior to step 1 registration; diagnostic thoracotomies and laparoscopies are not considered major surgeries
• Patients must not have any anticancer therapy or investigational agent within 28 days prior to step 1 registration
• Absolute neutrophil count (ANC) >= 1,500/mcl (documented within 28 days prior to step 1 registration)
• Hemoglobin >= 9 g/dl (documented within 28 days prior to step 1 registration)
• Platelets >= 100,000/mcl (documented within 28 days prior to step 1 registration)
• Creatinine =< 1.5 x upper limit of normal (ULN) (documented within 28 days prior to step 1 registration)
• Creatinine clearance >= 45 ml/min (documented within 28 days prior to step 1 registration)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 28 days prior to step 1 registration)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (within 28 days prior to step 1 registration)
• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years
• Patients must not be pregnant or nursing due to the potential teratogenic side effects of the protocol treatment; women of reproductive potential and men must have agreed to use an effective contraceptive method for the duration of study treatment and for 5 months (150 days) after the last dose of atezolizumab; 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 patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
• Patient must NOT have a history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Patient must NOT have a known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
• Patients must not have severe infections within 28 days prior to step 1 registration, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• Patients must not have active autoimmune disease that has required systemic treatment in 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
• Patients must not have undergone prior allogeneic bone marrow transplantation or prior solid organ transplantation
• Patient must not have active tuberculosis
• Patient must not have history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis; this protocol includes an immunotherapy agent which can precipitate known pneumonitis
• Patient must not have active (chronic or acute) hepatitis B virus (HBV) infection as evidenced by testing performed within 28 days prior to registration; patients with past or resolved HBV infection are eligible; active HBV is defined as having a positive hepatitis B surface antigen (HBsAg) test; past or resolved HBV is defined as having a negative HBsAG test and a positive total hepatitis B core antibody (HBcAb) test; patient must not have active hepatitis C virus (HCV) infection as evidenced by testing performed within 28 days prior to registration; active HCV is defined as having a positive HCV antibody test followed by a positive HCV RNA test
• Patient must NOT have a known positive test for human immunodeficiency virus (HIV); patients do not need to be screened for HIV; patients with HIV are excluded due to a potential incompetent immune system and need for medications that could interfere with the treatment and immunotherapy
• Patient must not have significant cardiovascular disease, such as New York Heart Association cardiac disease (class II or greater), myocardial infarction within 3 months prior to initiation of treatment, unstable arrhythmias, or unstable angina given the higher risks associated with surgical resection
• Patient must not receive live, attenuated influenza vaccine within 4 weeks prior to registration or at any time during the study and until 5 months after the last dose of atezolizumab
• Patient must be willing to have tissue specimens submitted for translational medicine studies
• Patient must be offered the opportunity to participate in tissue and blood banking for future studies
• Patient must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
• As a part of the Oncology Patient Enrollment Network (OPEN) registration process, the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
• STEP 2: SURGERY
• Patient must have a CT of chest/abdomen with contrast or FDG-PET/CT scan within 28 days prior to step 2 registration; patients must not have evidence of progression per RECIST 1.1 or modified RECIST for pleural tumors
• Patients planning to receive EPP must also be evaluated for appropriateness of radiation therapy (RT) by a radiation oncologist within 14 days prior to step 2 registration
• Patients must have a Zubrod performance status of 0-1 documented within 28 days prior to step 2 registration
• Patients must have postoperative predicted forced expiratory volume in 1 second (FEV1) > 35% prior to surgery obtained within 28 days prior to step 2 registration; pulmonary function tests to ascertain these values must be obtained within 28 days prior to Step 2 registration
• Patients must have postoperative predicted carbon monoxide diffusing capability (DLCO) > 35% prior to surgery obtained within 28 days prior to step 2 registration; pulmonary function tests to ascertain these values must be obtained within 28 days prior to Step 2 registration
• Patient must have received at least two cycles of triplet neoadjuvant therapy (all three drugs) during step 1
• Patient must be registered to step 2 no less than 21 days and no more than 90 days after the end of their final cycle of neoadjuvant therapy
• STEP 3: MAINTENANCE
• Patient must have received either P/D or EPP and must have recovered from all effects of surgery with adequate wound healing; patients who received radiation therapy (RT) must be registered to step 3 within 90 days after discontinuing RT; patients who did not receive RT must be registered to step 3 within 90 days after surgery
• Patient must have a CT of chest/abdomen/pelvis with contrast or FDG-PET/CT scan within 28 days prior to step 3 registration; patient must not have evidence of progression per RECIST 1.1 or modified RECIST for pleural tumors
• Patient may have discontinued RT early due to toxicity or other reasons
• Patients must have a Zubrod performance status of 0-1 documented within 28 days prior to step 3 registration
• ANC > 1,500/mcl (documented within 28 days prior to step 3 registration)
• Hemoglobin > 9 g/dl (documented within 28 days prior to step 3 registration)
• Platelets > 100,000/mcl (documented within 28 days prior to step 3 registration)
• Creatinine < 1.5 x ULN (documented within 28 days prior to step 3 registration)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 28 days prior to step 3 registration)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (within 28 days prior to step 3 registration)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (chemotherapy, surgery, RT); NEOADJUVANT: Patients receive atezolizumab IV over 30-60 minutes, pemetrexed disodium IV over 10 minutes, and cisplatin IV over 2 hours on day 1. Cycles repeats every 21 days for 4 cycles in the absence of disease progression or unexpected toxicity. SURGERY: Within 21-90 days after completion of neoadjuvant therapy, patients undergo EPP or PD. Patients who undergo EPP will then undergo RT. MAINTENANCE: Within 90 days after completion of either PD or radiation (post-EPP), patients receive atezolizumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 1 year in the absence of disease progression or unexpected toxicity.

Radiation: Radiation Therapy; Undergo RT; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Energy Type; 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: Pemetrexed Disodium; Given IV; Other Names: Alimta; LY231514; N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt; Almita; Drug: Atezolizumab; Given IV; Other Names: Tecentriq; MPDL3280A; RO5541267; RG7446; MPDL 3280A; MPDL 328OA; MPDL-3280A; MPDL328OA; Procedure: Extrapleural Pneumonectomy; Undergo EPP; Procedure: Pleurectomy; Undergo PD; Other Names: Excision of Pleura

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of Neoadjuvant Cisplatin-Pemetrexed-Atezolizumab, Surgery +/- Radiation, and Maintenance Therapy.	The number of participants who received at least two cycles of the triplet neoadjuvant therapy getting at least one dose of maintenance therapy.	Duration of treatment until first dose of maintenance therapy. Includes 21 day cycles of neoadjuvant chemo and surgery - extrapleural pneumonectomy or pleurectomy/decortication (radiation therapy for participants who received extrapleural pneumonectomy).
Safety of Neoadjuvant Cisplatin-Pemetrexed-Atezolizumab, Surgery +/- Radiation, and Maintenance Therapy.	The number of participants that experienced a Grade 4-5 immune-related adverse event. The regimen was considered safe if no participants experienced a Grade 4-5 immune-related AE.	Duration of treatment and follow-up until death or 3 years post Step 1 registration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	From date of registration to Step 1 to date of first documentation of progression by RECIST 1.1 and modified RECIST 1.1, symptomatic deterioration, or death due to any cause. Participants last known to be alive and progression free are censored at date of last disease assessment.	Duration of treatment and follow-up until death or 3 years post Step 1 registration.
Overall Survival (OS)	From date of initial registration to date of death due to any cause. Participants last known to be alive are censored at date of last contact.	3 years after the last accrual
Response Rate (RR)	Percentage of participants with confirmed and unconfirmed, complete and partial, defined by RECIST 1.1 and mRECIST for Pleural Tumors	Duration of treatment and follow-up until death or 3 years post Step 1 registration.

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Anne S Tsao, SWOG Cancer Research Network

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2018
• Primary Completion (Actual): October 1, 2022
• Study Completion (Estimated): September 21, 2024

Study Registration Dates

• First Submitted: July 24, 2017
• First Submitted That Met QC Criteria: July 24, 2017
• First Posted (Actual): July 25, 2017

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

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; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Cisplatin; Antibodies, Monoclonal; Pemetrexed; Atezolizumab
• Other Study ID Numbers: NCI-2017-01230 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180888 (U.S. NIH Grant/Contract); S1619 (Other Identifier: CTEP)

Drug and device information, study documents

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