Genomic and Methylation Markers in SCLC and LCNEC for Chemo-Immunotherapy Resistance Prediction (STRATUS)

Summary

The goal of this observational study is to understand how genomic and epigenetic factors contribute to resistance against chemo-immunotherapy in adults diagnosed with extensive-stage small cell lung cancer (ES-SCLC) or metastatic large cell neuroendocrine carcinoma (LCNEC). Both ES-SCLC and LCNEC are aggressive forms of lung cancer with limited treatment options and poor prognosis. While initial responses to chemo-immunotherapy are often promising, most patients develop resistance within a few months, resulting in disease progression and limited survival. This study seeks to explore the molecular and cellular changes that drive resistance, providing insights that could guide more personalized and effective treatment strategies in the future.

The study focuses on identifying genomic and methylation signatures, as well as analyzing circulating tumor cells (CTCs) and tumor DNA (ctDNA), to better understand the mechanisms of resistance. By collecting and analyzing these biomarkers over time, researchers aim to identify patterns that distinguish patients who benefit long-term from therapy from those who experience early resistance. These findings may pave the way for new diagnostic tools and therapies to predict and overcome resistance to chemo-immunotherapy.

The main questions this study seeks to answer are:

Are there specific genomic or methylation patterns that predict resistance to chemo-immunotherapy in ES-SCLC and LCNEC? How are circulating tumor cells (CTCs) and tumor DNA (ctDNA) associated with disease progression, treatment response, and survival? What molecular differences exist between patients who respond long-term and those who develop resistance early in their treatment?

Participants will:

Provide blood and tumor tissue samples before treatment to establish baseline molecular profiles.

Undergo follow-up visits every 9 weeks during treatment, where additional blood samples and imaging tests will be collected to monitor disease progression and treatment response.

Optionally provide tissue samples through re-biopsy if the disease progresses, enabling researchers to compare changes in tumor biology over time.

All blood and tissue samples will be de-identified and securely stored for genomic and epigenetic analyses. Blood samples will be examined for circulating tumor cells and tumor DNA, while tumor tissue samples will undergo in-depth genomic and methylation profiling. Researchers will use advanced molecular and bioinformatics techniques to uncover specific patterns associated with resistance, aiming to improve current treatment strategies and develop more precise therapies.

The study will analyze data from patients over three years, encompassing various stages of treatment and disease progression. By examining longitudinal samples, the study aims to capture the dynamic changes that occur in the tumor microenvironment and how these relate to treatment outcomes.

This research is particularly important because current treatment options for ES-SCLC and LCNEC are limited, and there are no established methods to predict which patients will respond to chemo-immunotherapy. Identifying biomarkers of resistance could transform clinical care, allowing oncologists to tailor treatments to individual patients' molecular profiles and improve survival outcomes.

Ultimately, the findings from this study could lead to the development of new biomarkers for resistance, improve early detection of treatment failure, and provide the foundation for novel therapies targeting resistant cancer cells. By addressing a critical gap in the understanding of resistance mechanisms, the STRATUS trial has the potential to significantly advance the field of personalized oncology.

Conditions

• Small Cell Lung Cancer
• Large Cell Neuroendocrine (NE) Tumors
• Treatment Failure
• Biomarkers / Blood
• Biomarkers
• Immunotherapy

Interventions

DRUG

Carboplatin/Cisplatin -Etoposide - Atezolizumab

This intervention represents the standard-of-care first-line treatment regimen for extensive-stage small cell lung cancer (ES-SCLC). The regimen includes: Carboplatin or Cisplatin: Platinum-based chemotherapeutic agents that cause DNA cross-linking, leading to tumor cell death. Etoposide: A topoisomerase II inhibitor that prevents DNA replication and tumor growth. Atezolizumab: A PD-L1 immune checkpoint inhibitor that enhances the immune system's ability to detect and destroy cancer cells. This combination therapy is administered as part of routine clinical practice. The study does not investigate the efficacy or safety of these drugs but rather focuses on analyzing molecular changes in tumors, such as genomic and epigenetic alterations, to understand mechanisms of treatment resistance. Biospecimens are collected from patients during treatment and progression for detailed analysis.

Sponsors & Collaborators

• National and Kapodistrian University of Athens

  collaborator OTHER

• Icahn School of Medicine at Mount Sinai

  collaborator OTHER

• Sotiria General Hospital

  collaborator OTHER

• Oncology Center of Biochemical Education And Research

  lead OTHER

Eligibility

Min Age

18 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-02-20

Primary Completion

2028-03-20

Completion

2028-12-01

FDA Drug

Yes

Countries

• United States
• Greece

Study Locations