NCT02599454

Atezolizumab and Stereotactic Body Radiation Therapy in Treating Patients With Non-small Cell Lung Cancer

A Phase I Trial of an Immune Checkpoint Inhibitor Plus Stereotactic Ablative Radiotherapy in Patients With Inoperable Stage I Non-Small Cell Lung Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Megan Daly, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of atezolizumab that can be given together with stereotactic body radiation therapy (SBRT) in treating patients with stage I non-small cell lung cancer that cannot be removed by surgery. Monoclonal antibodies, such as atezolizumab, 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. Stereotactic body radiation therapy is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may kill more tumor cells and cause less damage to normal tissue. Giving atezolizumab together with stereotactic body radiation therapy may kill more tumor cells and be a better treatment for non-small cell lung cancer that cannot be removed by surgery.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of MPDL3280A (atezolizumab) that can be given with stereotactic ablative radiotherapy (SAR) (stereotactic body radiation therapy) in patients with inoperable stage I non-small cell lung cancer (NSCLC). SECONDARY OBJECTIVES: I. To characterize the safety profile of this regimen using CTCAE v4 (Common Toxicity Criteria for Adverse Events version 4). II. To provide preliminary efficacy data of the combination as determine by objective response rate and disease free survival using RECIST 1.1 (Response Evaluation Criteria for Solid Tumors) and Immune Related RECIST (irRECIST). TERTIARY OBJECTIVES: I. To analyze serial blood for change in cytokine signatures, fluorescence activated cell sorting (FACS) and immunophenotyping of peripheral blood mononuclear cells (PBMCs) and tumor infiltrating immune cells. II. To evaluate pre and post treatment tumor tissue (if available) for programmed cell death-ligand 1 (PD-L1) and other immune proteins in the tumor and tumor microenvironment and for molecular profiling in a subset of patient samples. III. To discover biomarkers of response from the data obtained. OUTLINE: This is a dose-escalation study of atezolizumab. DOSE ESCALATION PHASE: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Within 24-48 hours after receiving atezolizumab, patients also undergo 4-5 fractions of stereotactic body radiation therapy over days 1-5 of course 3. EXPANSION PHASE: Patients receive atezolizumab IV over 30-60 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Within 24-48 hours after receiving atezolizumab, patients also undergo 4-5 fractions of stereotactic body radiation therapy over days 1-5 of course 3. After completion of study treatment, patients are followed up at 30 days, every 3 months for 2 years, and then every 6 months for 3 years.

Conditions

• Stage I Non-Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Atezolizumab	Into the vein Day 1 every 3 weeks for 6 cycles
RADIATION	Stereotactic Body Radiation Therapy	Radiation therapy will be performed to 50 Gy over 4 fractions of 12/5 Gy each for peripherally located tumors and 50 Gy over 5 fractions of 10 Gy each for centrally located tumors

Timeline

• Start date: 2018-04-26
• Primary completion: 2019-12-27
• Completion: 2024-02-20
• First posted: 2015-11-06
• Last updated: 2025-10-27

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study