Resumen

This phase II/III trial compares the effect of adding radiation therapy to the usual maintenance therapy with atezolizumab versus atezolizumab alone in patients who have already received atezolizumab plus chemotherapy for the treatment of small cell lung cancer that has spread outside of the lung or to other parts of the body (extensive stage). 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. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radiation therapy in addition to atezolizumab may extend the time without extensive small cell lung cancer growing or spreading compared to atezolizumab alone.

Edad: 18 años o más

Género: Todos

Fecha de inicio: 01/07/2021

Fecha de finalización principal (estimada): 04/30/2027

Fecha estimada de finalización del estudio: 04/30/2027

Acepta voluntarios sanos: No

Propósito y descripción del ensayo

PRIMARY OBJECTIVES: I. To compare investigator-assessed progression free survival (PFS) between atezolizumab plus radiotherapy and atezolizumab alone. (Phase II) II. To compare overall survival (OS) between atezolizumab plus radiotherapy and atezolizumab alone. (Phase III) SECONDARY OBJECTIVES: I. To assess the toxicity between the atezolizumab plus radiotherapy arm and the atezolizumab arm. II. To assess the impact of adding radiotherapy on PFS and OS in patients with 1-3 visible tumors and \> 3 visible tumors. III. To assess the impact of adding radiotherapy on PFS and OS in patients receiving consolidation radiotherapy to all visible disease ("complete consolidation") and patients who do not receive consolidation radiation to all visible disease ("incomplete consolidation"). EXPLORATORY OBJECTIVE: I. To assess the association between pre-treatment tumor burden (determined by central radiographic assessment, using both tumor number and tumor volume), and PFS and OS benefit. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive atezolizumab intravenously (IV) over 30 minutes +/- 10 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive atezolizumab IV over 30 minutes +/- 10 minutes. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo radiation therapy once daily (QD) on days 1-5 during weeks 1-5 only. Patients undergo positron emission tomography and computed tomography (PET/CT) scan, computed tomography (CT), and magnetic resonance imaging (MRI) throughout the trial. Patients also undergo blood and tissue collection throughout the trial. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Criterios de elegibilidad

Edad: 18 años o más

Género: Todos

Acepta voluntarios sanos: No

Criterios de inclusión:

* Any confirmation (cytologic, histologic, or pathologic) of extensive stage small cell lung cancer at any site, either primary or metastases

* Partial response (PR) or stable disease (SD) after 4-6 cycles of etoposide/platinum (E/P) doublet plus atezolizumab by re-staging scans (positron emission tomography \[PET\]/computed tomography \[CT\] scan, diagnostic CT scan, magnetic resonance imaging \[MRI\] optional per treating physician); atezolizumab should continue through randomization. Patients must be randomized within 9 weeks of last dose of etoposide/platinum (if not receiving PCI) or 6 weeks from completion of prophylactic cranial irradiation (PCI)

* NOTE: Patients must have at least 3 cycles of E/P plus atezolizumab. They can have one cycle of induction E/P without concurrent atezolizumab if unable to receive concurrent E/P combined with atezolizumab for all cycles of induction therapy

* Patients must have measurable disease (per Response Evaluation Criteria in Solid Tumors \[RECIST\]) and 3 or fewer observable liver metastases and no evidence of progressive disease (per RECIST) at time of enrollment

* At time of enrollment after induction E/P chemotherapy and atezolizumab, if there is a pleural effusion, patients will be eligible if thoracentesis is cytologically negative 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

* Etapa apropiada para el ingreso al estudio según el siguiente proceso diagnóstico:

* History/physical examination within 14 days prior to registration;

* Imaging within 42 days prior to registration to include:

* MRI brain with contrast or CT brain with contrast

* CT chest, abdomen and pelvis or whole body PET/CT scan any time after the fourth cycle of chemotherapy and prior to registration

* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 14 days prior to registration

* Absolute neutrophil count (ANC) \>= 1,000/cells/mm\^3 (within 14 days prior to registration)

* Platelets \>= 75,000 cells/mm\^3 (within 14 days prior to registration)

* Hemoglobin \>= 8 g/dL (within 14 days prior to registration)

* Total bilirubin =\< 1.5 x upper limit of normal (ULN) (within 14 days prior to registration)

* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x ULN (AST and/or ALT =\< 5 ULN for patients with liver involvement) (within 14 days prior to registration)

* Alkaline phosphatase =\< 2.5 x ULN (=\< 5 ULN for patients with documented liver involvement or bone metastases) (within 14 days prior to registration)

* Adequate renal function = Creatinine clearance \>=40 mL/min by the Cockcroft-Gault (C-G) equation: (within 14 days prior to registration)

* Upfront radiation therapy of symptomatic metastatic site is permissible if causing symptoms such as pain or impending fracture

* Patients with brain metastases are eligible after receiving whole brain radiation before enrollment (anytime during induction systemic therapy). Whole brain radiation can be delivered with hippocampal sparing or 3-D conformal technique. Patients with irradiated brain metastases are eligible if they are clinically stable from a neurological standpoint after completing radiotherapy (e.g. not having uncontrolled seizures) and do not require use of steroids above a dose of 10 mg of prednisone daily

* For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to registration.

* Note: Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

* Mujeres \< Se considerará que una mujer de 50 años de edad se encuentra en la etapa posmenopáusica si ha estado amenorreica durante 12 meses o más después de la interrupción de los tratamientos hormonales exógenos y si sus niveles de hormona luteinizante y hormona foliculoestimulante se encuentran dentro del rango posmenopáusico establecido por la institución o si se sometió a una esterilización quirúrgica (ooforectomía bilateral o histerectomía).

* Se considerará que las mujeres mayores de 50 años son posmenopáusicas si han estado amenorreicas durante 12 meses o más después de la interrupción de todos los tratamientos hormonales exógenos, si han tenido menopausia inducida por radiación con la última menstruación hace más de 1 año, si han tenido menopausia inducida por quimioterapia con la última menstruación hace más de 1 año, o si se han sometido a esterilización quirúrgica (ooforectomía bilateral, salpingectomía bilateral o histerectomía).

* Patients positive for human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months and a stable regimen of highly active anti-retroviral (HAART) HIV-positive patients must have no requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections

* El paciente o un representante legalmente autorizado debe proporcionar el consentimiento informado específico para el estudio antes de ingresar al mismo.

Criterios de exclusión:

* Metastatic disease invading the liver (\> 3 metastases), heart or \> 10 metastatic sites detectable after induction systemic therapy. Each visible bone metastasis on radiographic scan counts as one site

* Patients with a concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen with atezolizumab or radiation

* Prior radiotherapy in the thorax that would result in overlapping RT fields, unless the overlapping fields meet acceptable dose constraints for normal tissue

* Active autoimmune disease, including, but not limited to: systemic lupus erythematosus; rheumatoid arthritis; inflammatory bowel disease (e.g. Crohn's, ulcerative colitis); vascular thrombosis associated with antiphospholipid syndrome; Wegener's granulomatosis; Sjogren's syndrome; Guillain-Barre syndrome; multiple sclerosis; vasculitis; or glomerulonephritis.

* If the autoimmune disease is not active for over 3 years and the patient is not receiving immunosuppressive treatment such as methotrexate or steroids above a dose equivalent to 10 mg prednisone daily, the patient is eligible.

* Los pacientes con antecedentes de hipotiroidismo autoinmune que reciben una dosis estable de hormona tiroidea de reemplazo son elegibles.

* Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible

* Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations are excluded only if they have active disease with acute exacerbation and on immunosuppressive medications within the 12 months prior to enrollment. They are eligible otherwise.

* Comorbilidad grave y activa definida de la siguiente manera:

* 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;

* Enfermedad hepática clínicamente significativa conocida, incluyendo hepatitis viral activa, alcohólica u otra; cirrosis; hígado graso; y enfermedad hepática hereditaria.

* Los pacientes con infección por hepatitis B pasada o resuelta (definida como tener una prueba de antígeno de superficie de la hepatitis B [HBsAg] negativa y una prueba de anticuerpos anti-HBc [anticuerpo contra el antígeno central de la hepatitis B] positiva) son elegibles.

* 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;

* History of recent myocardial infarction within 6 months prior to registration.

* Enfermedad pulmonar intersticial clínicamente significativa

* Pregnancy: Administration of atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 5 months (150 days) after the last dose of study agent. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

* Women who are breastfeeding and unwilling to discontinue

* Antecedentes de trasplante de órganos alogénicos

* Patients who have had immunotherapy-induced pneumonitis