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LIMITED STAGE SMALL CELL LUNG CANCER (LS-SCLC): A PHASE III RANDOMIZED STUDY OF CHEMORADIATION VERSUS CHEMORADIATION PLUS ATEZOLIZUMAB (NRG-LU005)

Chemoradiation With or Without Atezolizumab in Treating Patients With Limited Stage Small Cell Lung Cancer (NRG-LU005)

Kagamu Hiroshi

Saitama Medical University International Medical Center

1397-1 Yamane, Hidaka-shi, Saitama

nrg-lu005@a2healthcare.com

Ochiai Ayumi

A2 Healthcare Corporation

1-4-1, Koishikawa, Bunkyo-ku, Tokyo

+81-3-3830-1171

nrg-lu005@a2healthcare.com

Not Recruiting

April. 01, 2021

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

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 and CT abdomen with IV contrast (unless contraindicated based on kidney
function*) within 60 days prior to registration; MRI abdomen with IV contrast
allowed in place of CT abdomen.

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
ANC >=1,500/cells/mm3
Platelet Count >=100,000 cells/mm3
Hemoglobin >=9 g/dL
Total Bilirubin <=1.5 x ULN
AST (SGOT) and ALT (SGPT) <=2.0 x ULN

Adequate renal function within 30 days prior to registration defined as follows:
Creatinine clearance >= 30 mL/min by the Cockcroft-Gault (C-G) equation:

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

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 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

Both

Limited Stage Small Cell Lung Cancer (LS-SCLC)

Chemoradiation (Cisplatin 60 mg/m2/d + Etoposide 120 mg/m2/d or Carboplatin AUC = 5 mg/min/mL + Etoposide 100 mg/m2/d q3 weeks x 4 cycles)(Thoracic RT 45 Gy bid or 66 Gy daily beginning with cycle 2 of chemotherapy) +/- atezolizumab (1200 mg) q3 weeks x 1 year (17 doses), beginning with cycle 2 of chemotherapy

D055752

The primary endpoint is overall survival (OS), which is defined as the time from randomization to the date of death due to any cause.

PFS

Incidence of adverse events

Objective response rate (ORR) [ Time Frame: Up to 5 years ]

Local control [ Time Frame: Up to 5 years ]

Distant metastases-free survival (DMFS)

Quality of life (QoL) [ Time Frame: Up to 15 months after the end of the 4th cycle of chemotherapy ]

Quality-adjusted survival [ Time Frame: Up to 2 years ]

Level of fatigue [ Time Frame: Up to 2 years ]

Blood based tumor mutational burden (bTMB) and tissue-based tumor mutational burden (tTMB) [ Time Frame: Up to 5 years ]

Other Outcome Measures:
Patient-reported symptomatic toxicities [ Time Frame: Up to 15 months after completion of chemoradiation therapy ]

+81-42-984-4523

Mar. 24, 2021

No

USA/Canada