Title
A Randomized, Multi-Cohort Phase II Trial of Temozolomide and Atezolizumab as Second or Third Line Treatment for Small Cell Lung Cancer Big Ten Cancer Research Consortium BTCRC-LUN20-462

Description
This phase II trial studies the effects of temozolomide and atezolizumab as second line treatment for patients with small cell lung cancer that has spread to other places in the body (metastatic) or has come back (recurrent). Chemotherapy drugs, such as temozolomide, 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. 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 temozolomide and atezolizumab as second line treatment may help prolong survival in patients with small cell lung cancer.

Objective
Primary Objective: The primary objective is to estimate the efficacy of atezolizumab and temozolomide in two dosing schedules for patients with metastatic SCLC who progress after first line chemoimmunotherapy.

Secondary Objectives
1) To evaluate the safety profile and toxicity of combination atezolizumab and temozolomide in two dosing schedules as per CTCAE v 5.0
2) To evaluate the progression free survival (PFS) and overall survival (OS) of patients treated with combination atezolizumab and temozolomide
3) To evaluate the intracranial PFS rate at 6 months (icPFS6) of patients with SCLC treated with atezolizumab and temozolomide

Correlative/Exploratory Objectives
1) Explore association of MDSC levels at baseline biomarker status from tumor biopsy samples and peripheral blood and correlate these with clinical parameters (including ORR, OS and toxicity)
2) To evaluate changes in MDSC induced by different dosing of temozolomide
3) To explore post-translational modifications of PD-L1 by mass spectrometry

Treatment Experimental: Cohort I (atezolizumab, temozolomide)
Patients receive atezolizumab IV over 30-60 minutes on day 1 and temozolomide PO QD on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Experimental: Cohort II (atezolizumab, temozolomide)
Patients receive atezolizumab IV over 30-60 minutes on day 1. Patients also receive temozolomide PO QD on days 1-14 of cycle 1 and days 1-21 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Lung

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital