Limited Stage Small Cell Lung Cancer (LS-SCLC): A Phase III Randomized Study of Chemoradiation Versus Chemoradiation Plus Atezolizumab

Plain English Summary

Testing the Addition of a New Immunotherapy Drug, Atezolizumab (MPDL3280A), to the Usual Chemoradiation (CRT) Therapy Treatment for Limited Stage Small Cell Lung Cancer (LS-SCLC) is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Limited Stage Lung Small Cell Carcinoma, Stage I Lung Cancer AJCC v8, Stage II Lung Cancer AJCC v8, Stage III Lung Cancer AJCC v8. This trial compares standard chemoradiation with and without a new immunotherapy drug, atezolizumab, for limited stage small cell lung cancer. It's for patients with limited stage small cell lung cancer who have completed one cycle of chemotherapy. Participants will receive either chemoradiation alone or chemoradiation plus atezolizumab. They will be monitored for survival and tumor response. There are several treatment options available, including standard chemoradiation and other immunotherapies. The trial aims to enroll 544 participants.

Official Summary

This phase 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible patients must have a confirmed diagnosis of limited stage small cell lung cancer and have completed one cycle of chemotherapy. Patients must be at least 18 years old and in good general health. They must have measurable disease and meet certain blood and organ function criteria. Those with active autoimmune diseases or prior atezolizumab use are not eligible. This trial is studying Limited Stage Lung Small Cell Carcinoma, Stage I Lung Cancer AJCC v8, Stage II Lung Cancer AJCC v8, Stage III Lung Cancer AJCC v8, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures, such as overall survival, will provide critical data on the effectiveness of the new treatment approach for patients. The specific primary outcome measures are: Overall Survival (Randomization to date of death due or last follow-up. Median follow-up at the time of analysis was 23.8 months.). 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 aims to fill a treatment gap by evaluating the potential benefits of adding a new immunotherapy to standard chemoradiation for limited stage small cell lung cancer. 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 Limited Stage Lung Small Cell Carcinoma, Stage I Lung Cancer AJCC v8, Stage II Lung Cancer AJCC v8, Stage III Lung Cancer AJCC v8, where improved treatment options are needed.

Investor Insight

The large market size and high unmet need in small cell lung cancer make this trial significant, with a competitive landscape that includes other immunotherapies and chemotherapies. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 544 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor about your eligibility and the potential benefits and risks of participating in this trial. Undergo the standard chemoradiation or chemoradiation plus atezolizumab as directed by the study team. 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: 544 participants

Interventions

• RADIATION: 3-Dimensional Conformal Radiation Therapy — Undergo 3D-CRT
• DRUG: Atezolizumab — Given IV
• PROCEDURE: Biospecimen Collection — Correlative studies
• DRUG: Carboplatin — Given IV
• DRUG: Cisplatin — Given IV

Primary Outcomes

• Overall Survival (Randomization to date of death due or last follow-up. Median follow-up at the time of analysis was 23.8 months.)

Secondary Outcomes

• Progression Free Survival (PFS) (From randomization to progression or death due to any cause, whichever occurs first, or last tumor assessment if alive. MMedian follow-up at the time of analysis was 23.8 months.)
• Number of Participants by Highest Grade Adverse Event Reported (Randomization to last follow-up. Median follow-up at the time of analysis was 23.8 months.)
• Percentage of Participants With Confirmed Objective Response (Objective Response Rate (ORR)) (Randomization to last radiographic tumor assessment. Median follow-up at the time of analysis was 23.8 months.)
• Percentage of Participants With Local Progression (From randomization to local progression, other progression, or death, whichever occurs first, or last tumor assessment if alive. Median follow-up at the time of analysis was 23.8 months. 1-, 2-, and 3-year rates are reported.)
• Distant Metastases-free Survival (DMFS) (Randomization to DMFS event or local progression, whichever occurs first, or last tumor assessment if alive. Median follow-up at the time of analysis was 23.8 months.)

Full Eligibility 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 pre-registration 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; magnetic resonance imaging (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
  * 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
* Age \>= 18
* 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)
* 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

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 labo

Trial Locations

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• Fairbanks Memorial Hospital, Fairbanks, Alaska, United States
• Banner MD Anderson Cancer Center, Gilbert, Arizona, United States
• CTCA at Western Regional Medical Center, Goodyear, Arizona, United States
• Banner University Medical Center - Tucson, Tucson, Arizona, United States
• University of Arizona Cancer Center-North Campus, Tucson, Arizona, 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
• Sutter Auburn Faith Hospital, Auburn, California, United States
• Alta Bates Summit Medical Center-Herrick Campus, Berkeley, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Limited Stage Small Cell Lung Cancer
• Stage I Lung Cancer
• Stage II Lung Cancer
• Stage III Lung Cancer
• Immunotherapy
• Chemotherapy
• Radiation Therapy
• Small Cell Lung Carcinoma
• Lung Cancer
• Cancer Treatment

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