Call us 24/7

NRG-LU005: Limited stage small cell lung cancer (LS-SCLC): A phase II/III, randomized study of chemoradiation versus chemoradiation plus atezolizumab

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.

Status

Accepting new patients

Primary Study Objective(s)

The primary objectives of this study are to determine:

  • In phase II, progression-free survival (PFS)

To be determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will compare the distributions of PFS between treatment arms using a one-sided stratified log-rank test in all randomized eligible patients. The rates at various timepoints (e.g., every six months after randomization) and medians of PFS for each arm will be estimated using the Kaplan-Meier method (1958). The associated 95 percent confidence interval (CI) will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Results from an unstratified analysis will also be provided.

  • In phase III, overall survival (OS)

The primary hypotheses for the phase II and III portions will be evaluated by comparing arm 1 to arm 2 based on PFS (phase II) and OS (phase III) using a stratified log-rank test. Hazard ratios will be estimated using a stratified Cox regression model. Event rates over time will be estimated within each treatment group using the Kaplan-Meier method.

Core eligibility

Note: This is only a partial list of eligibility criteria.

Including patients who:

  • Have 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, eighth edition [Ed.]), within 60 days prior to registration
  • Have received one cycle of platinum/etoposide chemotherapy prior to study registration, with study registration required within 21 days from day one of first cycle of chemotherapy and protocol treatment designed to begin 21 days after initiation of cycle one. (Note: If patient has not recovered from cycle one chemotherapy toxicities, then an additional 14 days is permitted.)
  • Have had measurable disease (per Response Evaluation Criteria in Solid Tumors [RECIST], version 1.1) prior to the required cycle of platinum/etoposide chemotherapy
  • Meet minimal staging requirements that 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
  • Have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 30 days prior to registration
  • Have the following:
    • Absolute neutrophil count (ANC)/granulocytes >= 1, 500/cells/mm^3 (pre-cycle one)
    • Platelet count >= 100,000 cells/mm^3 (pre-cycle one)
    • Hemoglobin >= 9 g/dL (pre-cycle one)
    • Total bilirubin =< 1.5 x upper limit of normal (ULN) (pre-cycle one)
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 x ULN (pre-cycle one)
    • 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)
  • Have a pleural effusion, 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
  • Have negative serum pregnancy test within 14 days of registration for pre-menopausal women of childbearing potential
  • Provide study-specific informed consent prior to study entry

Excluding patients who:

  • Have definitive clinical or radiologic evidence of metastatic disease
  • Have definitive surgical resection of small cell lung cancer
  • Had 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 two years (carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
  • Had more than one cycle of prior platinum-based chemotherapy for SCLC prior to enrollment; note that prior chemotherapy for a different cancer is allowable
  • Had 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
  • Have cytologically positive pleural or pericardial fluid
  • Have an active, known or suspected autoimmune disease. (Note: 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)
  • Have active or prior documented inflammatory bowel disease, such as Crohn's disease or  ulcerative colitis
  • Had an allogeneic organ transplant
  • Have a history of primary immunodeficiency
  • Have 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 three months
  • Transmural myocardial infarction within the last 3 months
  • Clinically significant interstitial lung disease
  • Have 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
  • Are 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) (Note: This exclusion is necessary because the treatment involved in this study may be significantly teratogenic.)
     

Accepting new patients

 

Learn more at

clinicaltrials.gov

 

Principal Investigator(s)

Bruce Gershenhorn

Patricia Rich

Shayma Master Kazmi

Theodore Pollock