Phase III Randomized Study of Chemoradiation Vs Chemoradiation + Atezolizumab

Criteria

Inclusion Criteria:

• Pathologically (histologically or cytologically) proven diagnosis of limited stage small cell lung cancer (Stage Tx, T1-T4, N0-3, 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 pre-registration (prior to study entry). Study registration must be within 21 days from day 1 of the pre-registration cycle of chemotherapy.
• 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 60 days prior to registration
  • CT chest/abdomen with IV contrast (unless contraindicated based on kidney function) within 60 days prior to registration;
    • Note: If contrast allergy exists, premedication per institutional guidelines should be performed prior to obtaining CT with contrast. The only exception to this is a documented life-threatening allergy
  • 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) >= 1, 500/cells/mm^3 (prior to pre-registration cycle)
• Platelet count >= 100,000 cells/mm^3 (prior to pre-registration cycle)
• Hemoglobin >= 9 g/dL (prior to pre-registration cycle)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (prior to pre-registration cycle)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 x ULN (prior to pre-registration cycle)
• Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2 (within 30 days prior to registration)
• 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
• Hepatitis B/C testing prior to enrollment for patients that have not been tested before. Note: This is required even if the patient has never shown or had symptoms of hepatitis
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

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
• Any prior atezolizumab or other immunotherapy agent
• 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. Note that if hepatitis status is unknown, hepatitis B/C testing is required
    • 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). (The HCV RNA test must be performed for patients who have a positive HCV antibody test.)
  • Known immunosuppressive disease, for example history of bone marrow transplant or chronic lymphocytic leukemia (CLL)
  • 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 180 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