A Randomized Phase III Trial of Induction/Consolidation Atezolizumab (NSC #783608) + SBRT Versus SBRT Alone in High Risk, Early Stage NSCLC

Plain English Summary

Testing the Addition of the Drug Atezolizumab to the Usual Radiation Treatment for Patients With Early Non-small Cell Lung Cancer is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Lung Non-Small Cell Carcinoma, Stage I Lung Cancer AJCC v8, Stage II Lung Cancer AJCC v8. This trial tests if adding a drug called atezolizumab to standard radiation therapy improves outcomes for early-stage lung cancer. It is for patients with high-risk, early-stage non-small cell lung cancer who cannot have surgery. Participation involves receiving either radiation therapy alone or radiation therapy combined with atezolizumab, and undergoing regular medical check-ups and tests. The main alternative for eligible patients is standard radiation therapy alone, as surgery is not an option. The trial aims to enroll 480 participants.

Official Summary

This phase III trial studies how well atezolizumab added to the usual radiation therapy works in treating patients with stage I-IIA non-small cell lung cancer. 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, such as stereotactic body radiation therapy, uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving atezolizumab and radiation therapy may work better than radiation therapy alone in treating patients with early non-small cell lung cancer.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with stage I-IIA non-small cell lung cancer (NSCLC) that has specific high-risk features and is not spreading to lymph nodes or other parts of the body. Patients must be at least 18 years old and medically unable or unwilling to undergo surgery. Individuals who have not received prior treatment for this cancer and do not have certain other medical conditions like active autoimmune disease or significant heart problems may be eligible. Patients with suspicious lymph nodes will need to have them sampled to confirm they are not involved by cancer. This trial is studying Lung Non-Small Cell Carcinoma, Stage I Lung Cancer AJCC v8, Stage II Lung Cancer AJCC v8, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome, overall survival, measures how long patients live after starting treatment, indicating if the new combination therapy helps patients live longer. The specific primary outcome measures are: Overall survival (From date of randomization to date of death due to any cause, assessed up to 3 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a gap in treatment for early-stage lung cancer patients who are not candidates for surgery, by investigating if immunotherapy can enhance the effectiveness of radiation therapy. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Lung Non-Small Cell Carcinoma, Stage I Lung Cancer AJCC v8, Stage II Lung Cancer AJCC v8, where improved treatment options are needed.

Investor Insight

This trial targets a significant market for early-stage lung cancer treatments, with atezolizumab being an established immunotherapy drug, suggesting a potentially favorable competitive landscape and Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if your specific type and stage of lung cancer qualifies for this trial and what the potential benefits and risks are for you. Understand that you will be randomly assigned to receive either the standard radiation therapy or the combination of radiation therapy and atezolizumab. Be prepared for regular visits for treatment, monitoring of your health, and collection of blood and imaging samples. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 480 participants

Interventions

• DRUG: Atezolizumab — Given IV
• PROCEDURE: Biospecimen Collection — Undergo blood sample collection
• PROCEDURE: Computed Tomography — Undergo CT or PET/CT
• OTHER: Fludeoxyglucose F-18 — Undergo FDG PET/CT
• PROCEDURE: Positron Emission Tomography — Undergo PET/CT

Primary Outcomes

• Overall survival (From date of randomization to date of death due to any cause, assessed up to 3 years)

Secondary Outcomes

• Progression free survival (From date of randomization to date of first documentation of progression or death due to any cause, assessed up to 5 years)
• Incidence of adverse events (Up to 5 years)

Full Eligibility Criteria

Inclusion Criteria:

* Patient must have histologically or cytologically proven stage I-IIA or limited T3N0M0 non-small cell lung cancer (NSCLC), without radiographic evidence of nodal or distant involvement (N0M0). Patient may have T3 disease with the exclusion of pericardial involvement. Patients with multifocal tumors with no more than two lesions confirmed or suspected to be synchronous early stage NSCLCs are eligible provided at least one lesion is histologically or cytologically proven to be NSCLC and meets one or more high-risk features
* Disease must have one or more of the following high-risk features:

  * Tumor diameter \>= 2 cm (inclusive of any non-solid, ground glass component) as assessed by diagnostic CT
  * Tumor standard uptake value (SUV) max \>= 6.2 as assessed by FDG PET/CT
  * Moderately differentiated, poorly differentiated, or undifferentiated histology
* Patient must have undergone diagnostic chest CT with or without contrast (IV contrast preferred) within 42 days prior to randomization. PET-CT may be used if the CT portion is of comparable diagnostic quality to a stand-alone CT. All disease must be assessed within 42 days prior to randomization
* Patient must have undergone FDG PET/CT of chest within 90 days prior to randomization
* Patient must not have evidence of hilar or mediastinal nodal involvement. Any patient with radiographically suspicious hilar or mediastinal nodes (including features such as non-calcified nodes with a short axis diameter \> 1 cm, abnormal morphology, and/or elevated FDG avidity) must undergo cytologic sampling of suspicious nodes to rule out involvement prior to randomization. Mediastinal nodal sampling for other patients is optional. For cases in which the treating physician/multidisciplinary opinion is used to define nodes as "non-suspicious" (such as long-standing, stable enlarged nodes from other medical causes), the rationale must be clearly documented within the medical record
* Patient must have undergone history and physical examination within 28 days prior to randomization
* Patient must be medically or surgically inoperable as documented by the evaluating thoracic surgeon or multi-disciplinary tumor board consensus OR patient's unwillingness to undergo surgical resection must be clearly documented
* Patient must not have received any prior treatment for the current NSCLC diagnosis
* Patient must not have undergone prior radiation to overlapping regions of the chest that, in the opinion of the treatment physician, will interfere with protocol treatment
* Patient must not have received treatment with systemic immunostimulatory or immunosuppressive agents, including corticosteroids, within 14 days prior to randomization
* Patient must be \>= 18 years old
* Patient must have Zubrod performance status of 0-2
* Patient must have adequate liver function defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x institutional upper level of normal (IULN) within 28 days prior to randomization
* Patient must have adequate renal function defined as calculated creatinine clearance \>= 30 mL/min using the following formula. The serum creatinine value used in the calculation must have been collected within 28 days prior to randomization
* Patient must have absolute neutrophil count (ANC), platelets, and hemoglobin measured within 28 days prior to randomization. The purpose of these tests is to collect baseline values to compare with on-treatment values
* Patient must have thyroid-stimulating hormone (TSH) measured within 28 days prior to randomization. The purpose of this test is to collect baseline values to compare with on-treatment values
* Patient must not have significant cardiovascular disease (New York Heart Association \[NYHA\] class II or greater)
* Patient must not have myocardial infarction within 90 days prior to randomization
* Patient must not have unstable arrhythmias or unstable angina
* Patient must not have known left ventricular ejection fraction (LVEF) \< 40% within 28 days prior to randomization

  * NOTE: Assessment of LVEF by echocardiogram or multigated acquisition (MUGA) is not an eligibility requirement, but if a standard of care echocardiogram or MUGA was clinically indicated, the LVEF must not be \< 40% within 28 days prior to randomization
* Patient must not have had an infection \>= grade 3 (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) within 28 days prior to randomization
* Patient must not have an active autoimmune disease that has required systemic treatment in past two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
* Patient must be tested for hepatitis B within 28 days prior to randomization. Patient must not have active (chron

Trial Locations

• Providence Alaska Medical Center, Anchorage, Alaska, United States
• NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro, Jonesboro, Arkansas, United States
• University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
• Kaiser Permanente-Deer Valley Medical Center, Antioch, California, United States
• AIS Cancer Center at San Joaquin Community Hospital, Bakersfield, California, United States
• Alta Bates Summit Medical Center-Herrick Campus, Berkeley, California, United States
• Tower Cancer Research Foundation, Beverly Hills, California, United States
• Kaiser Permanente Dublin, Dublin, California, United States
• Kaiser Permanente-Fremont, Fremont, California, United States
• Kaiser Permanente-Fresno, Fresno, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Lung Cancer
• Non-Small Cell Lung Cancer
• Stage I Lung Cancer
• Stage II Lung Cancer
• Early Stage Lung Cancer
• Thoracic Oncology
• Radiation Oncology
• Medical Oncology
• Immunotherapy
• Targeted Therapy

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