NCT06717243 · Oncology Center of Biochemical Education And Research
Genomic and Methylation Markers in SCLC and LCNEC for Chemo-Immunotherapy Resistance Prediction (STRATUS)
(STRATUS)
What this study is about
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.
View original scientific description
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.
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.
Primary outcome measures
Number of Participants with Genomic and Epigenetic Alterations Associated with Resistance to Chemo-Immunotherapy
Time frame: Baseline to disease progression (up to 36 months).
Identification of genomic, methylation, and other epigenetic alterations that are associated with resistance to standard-of-care chemo-immunotherapy (platinum-based chemotherapy combined with immune checkpoint inhibitors) in patients with extensive-stage small cell lung cancer (ES-SCLC) and metastatic large cell neuroendocrine carcinoma (LCNEC).
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Age: Adults aged 18-85 years.
- Histologically confirmed locally advanced extensive-stage small cell lung cancer (ES-SCLC).
- Histologically confirmed locally advanced or metastatic large cell neuroendocrine carcinoma (LCNEC).
- Treatment Plan: Eligible patients must be initiating standard-of-care chemo-immunotherapy, including platinum-based chemotherapy (cisplatin or carboplatin) combined with immune checkpoint inhibitors (atezolizumab or durvalumab).
- Measurable Disease: At least one measurable or evaluable lesion as defined by RECIST 1.1 criteria.
- Baseline Biospecimen Availability: Patients must agree to provide baseline blood and tumor biopsy samples for molecular and genomic analyses.
- Treatment Naïve for Study Indication: Patients should not have received prior systemic therapy for ES-SCLC or LCNEC.
- Life Expectancy: Estimated life expectancy of at least 3 months, as determined by the treating physician.
- Follow-Up Commitment: Willingness to attend scheduled follow-up visits and provide additional biospecimens (blood and/or tissue) during treatment and at progression.
- Performance Status: ECOG performance status of 0-2.
- Organ Function: Adequate hematologic, renal, and hepatic function as per the treating physician's discretion.
- Consent: Ability and willingness to provide written informed consent for participation in the study and collection of biospecimens (e.g., blood and tumor tissue).
- Compliance with Study Protocol: Demonstrated ability and willingness to comply with all study-related procedures, including biospecimen collection and follow-up visits.
- Non-Pregnant and Non-Lactating: Women of childbearing potential must have a negative pregnancy test at baseline and agree to use effective contraception during the study period.
- Immunotherapy Eligibility: Patients must not have contraindications to immune checkpoint inhibitors (e.g., autoimmune diseases requiring systemic immunosuppressive therapy).
- Platinum-Based Therapy Tolerance: Patients must be deemed medically fit to receive platinum-based chemotherapy (cisplatin or carboplatin) as determined by the treating physician.
- No Active Infections: Patients must not have active, uncontrolled infections, including but not limited to tuberculosis, hepatitis B, hepatitis C, or HIV.
- Psychosocial Stability: Patients must have adequate psychosocial support and the mental capacity to understand and provide informed consent for participation in the study.
- Stable Brain Metastases: Patients with brain metastases are eligible if the metastases have been treated (e.g., surgery or radiotherapy) and are stable for at least 4 weeks prior to enrollment, as confirmed by imaging.
- Steroid Use for Brain Metastases: Patients requiring corticosteroids for brain metastases are eligible only if they are on a stable or tapering dose equivalent to ≤10 mg/day of prednisone for at least 2 weeks prior to enrollment.
Exclusion criteria
- Uncontrolled Brain Metastases: Patients with untreated or progressive brain metastases causing significant neurological symptoms.
- Concurrent Malignancies: Presence of any active malignancy other than ES-SCLC or LCNEC within the past 3 years, except for treated non-melanoma skin cancer or in situ cervical carcinoma.
- Previous Systemic Therapy: Prior systemic chemotherapy or immunotherapy for ES-SCLC or LCNEC.
- Severe Comorbidities: Significant comorbidities, such as uncontrolled cardiovascular, respiratory, or autoimmune diseases, that could interfere with study participation or treatment.
- Active Infection: Patients with active infections requiring systemic therapy, including tuberculosis, hepatitis B or C, or HIV.
- Pregnancy or Lactation: Pregnant or lactating women, or women of childbearing potential who are not using effective contraception.
- Immunosuppressive Therapy: Patients requiring systemic immunosuppressive therapy, including high-dose corticosteroids (equivalent to \>10 mg/day prednisone), within 2 weeks prior to enrollment.
- Severe Allergic Reactions: History of severe hypersensitivity reactions to any component of the planned treatment regimen, including platinum-based chemotherapy or immune checkpoint inhibitors.
- Life-Threatening Conditions: Life expectancy less than 3 months, as assessed by the treating physician.
- Inability to Comply: Patients unable or unwilling to adhere to study protocols, including biospecimen collection and follow-up visits.
Where
- New York, New York
Collaborators
National and Kapodistrian University of Athens, Icahn School of Medicine at Mount Sinai, Sotiria General Hospital
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Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
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Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
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Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
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How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Mar 19, 2025 · Source of record for eligibility and locations