Chemoradiation with or without Atezolizumab in Treating Patients with Limited Stage Small Cell Lung Cancer

Status: Active

Description

This phase II / III trial studies how well chemotherapy and radiation therapy (chemoradiation) with or without atezolizumab works in treating patients with limited stage small cell lung cancer. Drugs used in chemotherapy, such as etoposide, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. 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. Giving chemoradiation with or without atezolizumab may work better in treating patients with limited stage small cell lung cancer.

Eligibility Criteria

Inclusion Criteria

  • Pathologically (histologically or cytologically) proven diagnosis of limited stage small cell lung cancer (Stage Tx, T1-T4, N1-3, M0, American Joint Committee on Cancer [AJCC] staging, 8th edition [Ed.]), within 60 days prior to registration
  • Patients must have received one cycle of platinum/etoposide chemotherapy prior to study registration, with study registration required within 21 days from day 1 of first cycle of chemotherapy and protocol treatment designed to begin 21 days after initiation of cycle 1. If patient has not recovered from cycle 1 chemotherapy toxicities, then an additional 14 days is permitted
  • Patients must have had measurable disease (per Response Evaluation Criteria in Solid Tumors [RECIST], version 1.1) prior to the required cycle of platinum/etoposide chemotherapy
  • Minimal staging requirements include: * History/physical examination within 30 days prior to registration * Positron emission tomography (PET)/computed tomography (CT) scan for staging within 45 days prior to registration * CT chest/abdomen with IV contrast (unless contraindicated based on kidney function) within 30 days prior to registration – this can be obtained as part of PET/CT if CT imaging is of diagnostic quality * Magnetic resonance imaging (MRI) scan of the brain with contrast (preferred) or CT scan of the brain with contrast (allowable if there is a contraindication with MRI with contrast) within 30 days prior to registration
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 30 days prior to registration
  • Absolute neutrophil count (ANC)/granulocytes >= 1, 500/cells/mm^3 (pre-cycle 1)
  • Platelet count >= 100,000 cells/mm^3 (pre-cycle 1)
  • Hemoglobin >= 9 g/dL (pre-cycle 1)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (pre-cycle 1)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 x ULN (pre-cycle 1)
  • Serum creatinine =< 1.5 x ULN OR calculated creatinine clearance >= 60 ml/min (for carboplatin: creatinine clearance [CrCl] >= 50 by Cockcroft-Gault) (pre-cycle 1)
  • Patients presenting with a pleural effusion will be eligible if thoracentesis is cytologically negative and non-bloody or if pleural fluid is too small a volume to effectively sample by thoracentesis and does not show increased metabolic activity on CT/PET imaging
  • Negative serum pregnancy test within 14 days of registration for pre-menopausal women of childbearing potential
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Exclusion Criteria

  • Definitive clinical or radiologic evidence of metastatic disease
  • Definitive surgical resection of small cell lung cancer
  • Prior invasive malignancy (except non-melanomatous skin cancer, localized prostate cancer, or any early stage cancer treated with curative intent resection) unless disease free for a minimum of 2 years (carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
  • More than 1 cycle of prior platinum-based chemotherapy for SCLC prior to enrollment; note that prior chemotherapy for a different cancer is allowable
  • Prior radiotherapy to the lungs or mediastinum that would result in clinically significant overlap of radiation therapy fields; prior tangent fields for breast cancer with minimal overlap with target volumes are allowed per approval of study principal investigators (PIs)
  • Patients with cytologically positive pleural or pericardial fluid are not eligible
  • An active, known or suspected autoimmune disease. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
  • Active or prior documented inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis)
  • History of allogeneic organ transplant
  • History of primary immunodeficiency
  • Severe, active co-morbidity defined as follows: * Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease * Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications * Active tuberculosis * Active hepatitis B (chronic or acute) or hepatitis C infection. Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg]) test, a positive anti-HBc (antibody to hepatitis B core antigen), and a negative viral deoxyribonucleic acid (DNA) test (only obtained if HBsAg is found positive) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA) * Known immunosuppressive disease, for example history of bone marrow transplant or chronic lymphocytic leukemia (CLL) * CD4 count < 200 cells/microliter. Note that patients who are human immunodeficiency virus (HIV) positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol * Chronic obstructive pulmonary disease (COPD) requiring chronic oral steroid therapy of > 10 mg prednisone daily or equivalent at the time of registration. Inhaled corticosteroids are not exclusionary * Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months * Transmural myocardial infarction within the last 3 months * Clinically significant interstitial lung disease
  • A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception for the duration of study treatment and for 150 days after the last dose of study drug (Arm 2); this exclusion is necessary because the treatment involved in this study may be significantly teratogenic

Locations & Contacts

Colorado

Colorado Springs
Penrose-Saint Francis Healthcare
Status: Active
Contact: Site Public Contact
Phone: 308-398-6518
Email: clinicaltrials@sfmc-gi.org

Florida

Gainesville
University of Florida Health Science Center - Gainesville
Status: Active
Contact: Site Public Contact
Phone: 352-273-8010
Email: cancer-center@ufl.edu

Georgia

Atlanta
Emory Saint Joseph's Hospital
Status: Active
Contact: Site Public Contact
Phone: 404-851-7115
Emory University Hospital / Winship Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 404-778-1868
Emory University Hospital Midtown
Status: Active
Contact: Site Public Contact
Phone: 888-946-7447
Grady Health System
Status: Active
Contact: Site Public Contact
Phone: 404-489-9164
Savannah
Memorial Health University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 912-350-7887
Email: clayter1@memorialhealth.com

Illinois

Chicago
University of Illinois
Status: Active
Contact: Site Public Contact
Phone: 312-355-3046
Danville
Carle on Vermilion
Status: Active
Contact: Site Public Contact
Phone: 800-446-5532
Email: Research@carle.com
Decatur
Decatur Memorial Hospital
Status: Active
Contact: Site Public Contact
Phone: 217-876-4740
Email: rhamrick@dmhhs.org
Effingham
Crossroads Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 217-876-4740
Email: rhamrick@dmhhs.org
Galesburg
Western Illinois Cancer Treatment Center
Status: Active
Contact: Site Public Contact
Phone: 309-344-2831
Ottawa
Illinois CancerCare-Ottawa Clinic
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Peoria
Illinois CancerCare-Peoria
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Methodist Medical Center of Illinois
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
OSF Saint Francis Medical Center
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
OSF Saint Francis Radiation Oncology at Peoria Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Peru
Illinois CancerCare-Peru
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Princeton
Illinois CancerCare-Princeton
Status: Active
Contact: Site Public Contact
Phone: 309-243-3605
Email: andersonj@illinoiscancercare.com
Springfield
Memorial Medical Center
Status: Active
Contact: Site Public Contact
Phone: 217-788-3528
Urbana
Carle Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-446-5532
Email: Research@carle.com

Indiana

Fort Wayne
Parkview Regional Medical Center
Status: Active
Contact: Site Public Contact
Phone: 877-784-4673

Iowa

Ames
McFarland Clinic PC - Ames
Status: Active
Contact: Site Public Contact
Phone: 515-956-4132
Clive
Medical Oncology and Hematology Associates-West Des Moines
Status: Active
Contact: Site Public Contact
Phone: 308-398-6518
Email: clinicaltrials@sfmc-gi.org
Mercy Cancer Center-West Lakes
Status: Active
Contact: Site Public Contact
Phone: 308-398-6518
Email: clinicaltrials@sfmc-gi.org
Des Moines
Medical Oncology and Hematology Associates-Laurel
Status: Active
Contact: Site Public Contact
Phone: 308-398-6518
Email: clinicaltrials@sfmc-gi.org
Mercy Medical Center - Des Moines
Status: Active
Contact: Site Public Contact
Phone: 308-398-6518
Email: clinicaltrials@sfmc-gi.org
West Des Moines
Mercy Medical Center-West Lakes
Status: Active
Contact: Site Public Contact
Phone: 308-398-6518
Email: clinicaltrials@sfmc-gi.org

Louisiana

Baton Rouge
Medical Center of Baton Rouge
Status: Active
Contact: Site Public Contact
Phone: 225-761-5346
Email: Camille.Beck@Ochsner.org
New Orleans
Ochsner Medical Center Jefferson
Status: Active
Contact: Site Public Contact
Phone: 504-703-8712
Email: Gregory.Johnstone@ochsner.org
University Medical Center New Orleans
Status: Active
Contact: Site Public Contact
Phone: 504-210-3539
Email: emede1@lsuhsc.edu

Maine

Belfast
Waldo County General Hospital
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 207-338-2500
Norway
Stephens Memorial Hospital
Status: Active
Contact: Site Public Contact
Phone: 207-396-8670
Email: OncClinicalResearch@mmc.org
Rockport
Penobscot Bay Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 207-396-8670
Email: ClinicalResearch@mmc.org
Sanford
MaineHealth / SMHC Cancer Care and Blood Disorders-Sanford
Status: Active
Contact: Site Public Contact
Email: LLemire@mmc.org
Scarborough
Maine Medical Center- Scarborough Campus
Status: Active
Contact: Site Public Contact
Phone: 207-396-8090
Email: wrighd@mmc.org
South Portland
Maine Medical Partners - South Portland
Status: Active
Contact: Site Public Contact
Phone: 207-396-8670
Email: ClinicalResearch@mmc.org

Michigan

Ann Arbor
Saint Joseph Mercy Hospital
Status: Active
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
Brighton
Saint Joseph Mercy Brighton
Status: Active
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
Canton
Saint Joseph Mercy Canton
Status: Active
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
Chelsea
Saint Joseph Mercy Chelsea
Status: Active
Contact: Site Public Contact
Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
Clarkston
21st Century Oncology MHP - Clarkston
Status: Active
Contact: Site Public Contact
Phone: 248-338-0663
Farmington Hills
21st Century Oncology MHP - Farmington
Status: Active
Contact: Site Public Contact
Phone: 248-338-0663
Troy
21st Century Oncology MHP - Troy
Status: Active
Contact: Site Public Contact
Phone: 248-338-0663

Missouri

Bonne Terre
Parkland Health Center-Bonne Terre
Status: Active
Contact: Site Public Contact
Phone: 314-996-5569
Cape Girardeau
Saint Francis Medical Center
Status: Active
Contact: Site Public Contact
Phone: 573-334-2230
Email: sfmc@sfmc.net
Jefferson City
Capital Region Southwest Campus
Status: Active
Contact: Site Public Contact
Phone: 573-632-4814
Email: swooden@mail.crmc.org
Saint Louis
Missouri Baptist Medical Center
Status: Active
Contact: Site Public Contact
Phone: 314-996-5569
Sainte Genevieve
Sainte Genevieve County Memorial Hospital
Status: Active
Contact: Site Public Contact
Phone: 314-996-5569
Sullivan
Missouri Baptist Sullivan Hospital
Status: Active
Contact: Site Public Contact
Phone: 314-996-5569
Sunset Hills
Missouri Baptist Outpatient Center-Sunset Hills
Status: Active
Contact: Site Public Contact
Phone: 314-996-5569

Nebraska

Grand Island
CHI Health Saint Francis
Status: Active
Contact: Site Public Contact
Phone: 308-398-6518
Email: clinicaltrials@sfmc-gi.org

Nevada

Las Vegas
OptumCare Cancer Care at Fort Apache
Status: Active
Contact: Site Public Contact
Phone: 702-384-0013
Email: research@sncrf.org
OptumCare Cancer Care at Oakey
Status: Active
Contact: Site Public Contact
Phone: 702-384-0013
Email: research@sncrf.org
Radiation Oncology Centers of Nevada Central
Status: Active
Contact: Site Public Contact
Phone: 702-384-0013
Email: research@sncrf.org
Reno
Renown Regional Medical Center
Status: Active
Contact: Site Public Contact
Phone: 702-384-0013
Email: research@sncrf.org

New York

Elmira
Arnot Ogden Medical Center / Falck Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 607-271-7000

North Carolina

Asheboro
Randolph Hospital
Status: Active
Contact: Site Public Contact
Phone: 336-832-0836
Email: vivian.sheidler@conehealth.com
Burlington
Cone Health Cancer Center at Alamance Regional
Status: Active
Contact: Site Public Contact
Phone: 336-538-7725
Email: kaye.shoffner@conehealth.com
Greensboro
Cone Health Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 336-832-0821
Email: vivian.sheidler@conehealth.com
Hendersonville
Margaret R Pardee Memorial Hospital
Status: Active
Contact: Site Public Contact
Phone: 828-696-4716
Email: karen.morris@unchealth.unc.edu
Kernersville
Novant Health Oncology Specialists-Kernersville
Status: Active
Contact: Site Public Contact
Phone: 336-718-8335
Email: asmarrs@novanthealth.org
Mount Airy
Novant Health Oncology Specialists-Mount Airy
Status: Active
Contact: Site Public Contact
Phone: 336-718-8335
Email: asmarrs@novanthealth.org
Pinehurst
FirstHealth of the Carolinas-Moore Regional Hospital
Status: Active
Contact: Site Public Contact
Phone: 910-715-3500
Email: jcwilliams@firsthealth.org
Stateville
Novant Health Oncology Specialists-Statesville
Status: Active
Contact: Site Public Contact
Phone: 336-718-8335
Email: asmarrs@novanthealth.org
Thomasville
Novant Health Oncology Specialists-Davidson County
Status: Active
Contact: Site Public Contact
Phone: 336-718-8335
Email: asmarrs@novanthealth.org
Wilkesboro
Novant Health Oncology Specialists-Wilkesboro
Status: Active
Contact: Site Public Contact
Phone: 336-718-8335
Email: asmarrs@novanthealth.org
Winston-Salem
Novant Health Forsyth Medical Center
Status: Active
Contact: Site Public Contact
Phone: 336-718-8335
Email: asmarrs@novanthealth.org

North Dakota

Grand Forks
Altru Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 701-780-6520

Ohio

Chillicothe
Adena Regional Medical Center
Status: Active
Contact: Site Public Contact
Phone: 877-779-7585
Email: sheree@columbusccop.org
Columbus
Doctors Hospital
Status: Active
Contact: Site Public Contact
Phone: 614-566-3275
Email: sheree@columbusccop.org
Grant Medical Center
Status: Active
Contact: Site Public Contact
Phone: 614-566-4475
Email: sheree@columbusccop.org
Mount Carmel East Hospital
Status: Active
Contact: Site Public Contact
Phone: 614-488-2118
Email: sheree@columbusccop.org
Mount Carmel Health Center West
Status: Active
Contact: Site Public Contact
Phone: 614-234-5433
Email: sheree@columbusccop.org
Riverside Methodist Hospital
Status: Active
Contact: Site Public Contact
Phone: 614-566-4475
Email: sheree@columbusccop.org
The Mark H Zangmeister Center
Status: Active
Contact: Site Public Contact
Phone: 614-488-2118
Email: sheree@columbusccop.org
Mansfield
OhioHealth Mansfield Hospital
Status: Active
Contact: Site Public Contact
Phone: 419-526-8018
Email: sheree@columbusccop.org
Marietta
Marietta Memorial Hospital
Status: Active
Contact: Site Public Contact
Phone: 800-523-3977
Email: sheree@columbusccop.org
Newark
Licking Memorial Hospital
Status: Active
Contact: Site Public Contact
Phone: 740-348-4000
Email: sheree@columbusccop.org
Portsmouth
Southern Ohio Medical Center
Status: Active
Contact: Site Public Contact
Phone: 614-488-2118
Email: sheree@columbusccop.org
Zanesville
Genesis Healthcare System Cancer Care Center
Status: Active
Contact: Site Public Contact
Phone: 740-454-5232
Email: sheree@columbusccop.org

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: Active
Contact: Site Public Contact
Phone: 405-271-8777
Email: ou-clinical-trials@ouhsc.edu
Tulsa
Cancer Treatment Centers of America
Status: Active
Contact: Site Public Contact
Phone: 412-339-5294
Email: Roster@nrgoncology.org

Oregon

Gresham
Legacy Mount Hood Medical Center
Status: Active
Contact: Site Public Contact
Phone: 503-413-2150
Portland
Legacy Good Samaritan Hospital and Medical Center
Status: Active
Contact: Site Public Contact
Phone: 800-220-4937
Email: cancer@lhs.org

Pennsylvania

Sayre
Guthrie Medical Group PC-Robert Packer Hospital
Status: Active
Contact: Site Public Contact
Phone: 800-836-0388
West Reading
Reading Hospital
Status: Active
Contact: Site Public Contact
Phone: 610-988-9323

Tennessee

Knoxville
Thompson Cancer Survival Center
Status: Active
Contact: Site Public Contact
Phone: 865-331-1812

Virginia

Fishersville
Augusta Health Center for Cancer and Blood Disorders
Status: Active
Contact: Site Public Contact
Phone: 540-332-5960

Washington

Vancouver
Legacy Salmon Creek Hospital
Status: Active
Contact: Site Public Contact
Phone: 503-413-2150

Wisconsin

Antigo
Langlade Hospital and Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 715-623-9869
Email: Juli.Alford@aspirus.org
La Crosse
Gundersen Lutheran Medical Center
Status: Active
Contact: Site Public Contact
Phone: 608-775-2385
Email: cancerctr@gundersenhealth.org
Wausau
Aspirus Regional Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-405-6866

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To compare progression free survival (PFS) for patients with limited stage small cell lung cancer (LS-SCLC) treated with chemoradiation +/- atezolizumab. (Phase II)

II. To compare overall survival (OS) for patients with LS-SCLC treated with chemoradiation +/- atezolizumab. (Phase III)

SECONDARY OBJECTIVES:

I. To compare progression free survival (PFS) for patients with limited stage small cell lung cancer (LS-SCLC) treated with chemoradiation +/- atezolizumab. (Phase III)

II. To determine overall response rate (ORR), rates of local control, and distant metastases free survival with chemoradiation +/- atezolizumab.

III. To characterize immune mediated and non-immune mediated toxicity from chemoradiotherapy plus atezolizumab.

IV. To compare quality of life, as measured by the Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI), for patients undergoing chemoradiation +/- atezolizumab.

V. To evaluate the quality-adjusted survival, using scores from the 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5L), of atezolizumab plus chemoradiotherapy with chemoradiotherapy for patients with LS-SCLC.

VI. To characterize fatigue, as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS), following chemoradiation +/- atezolizumab.

VII. To determine whether blood based tumor mutational burden (bTMB) and tissue-based tumor mutational burden (tTMB) predict for clinical outcomes.

EXPLORATORY OBJECTIVES:

I. To collect biospecimens at baseline and multiple timepoints throughout treatment and follow up, to allow for future analyses.

II. To characterize patient-reported symptomatic toxicities measured by the Patient-Reported Outcomes - Common Terminology Criteria for Adverse Evens (PRO-CTCAE).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive etoposide intravenously (IV) on days 1-3 and cisplatin IV or carboplatin IV on day 1. Cycles repeat every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) twice daily (BID) for approximately 3 weeks or once daily (QD) for approximately 6-7 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive treatment as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 or 2 of each chemotherapy cycle. Cycles repeat every 3 weeks for 17 cycles (1 year) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years.

Trial Phase & Type

Trial Phase

Phase II/III

Trial Type

Treatment

Lead Organization

Lead Organization
NRG Oncology

Principal Investigator
Kristin Ann Higgins

Trial IDs

Primary ID NRG-LU005
Secondary IDs NCI-2019-00178
Clinicaltrials.gov ID NCT03811002