Clinical trial NCT06049966: Atezolizumab in Large Cell Neuroendocrine Carcinoma
Official title: Effectiveness of Atezolizumab in Large Cell Neuroendocrine Carcinoma of the Lung and the Value of miR21 and miR-375 as Biomarkers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Large Cell Neuroendocrine Carcinoma of the Lung
Keywords: Atezolizumab
Immunotherapy
LCNEC
Large Cell Neuroendocrine Carcinoma
Immune Checkpoint Inhibitors
miR375
Lead sponsor: Oncology Center of Biochemical Education And Research
Sponsor class: OTHER
First posted: 2023-09-22
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Large Cell Neuroendocrine Carcinoma (LCNEC) is a rare and aggressive form of cancer that presents significant challenges regarding treatment options and prognosis. In this trial, the effectiveness of Atezolizumab in treating metastatic LCNEC was evaluated. Atezolizumab is an anti-PD-L1 antibody that has shown promising results in other types of cancer, such as small-cell lung Cancer and non-small-cell lung cancer. The trial aimed to assess the efficacy and safety of atezolizumab in combination with chemotherapy as a potential treatment option for treatment-naive patients with metastatic LCNEC The trial was conducted as an open-label, non-randomized study, comparing Atezolizumab plus platinum etoposide to platinum etoposide alone in patients with metastatic LCNEC.

Detailed description: This trial is a prospective clinical study to evaluate the effectiveness of a combination treatment regimen for patients with metastatic Large Cell Neuroendocrine Carcinoma (LCNEC) originating from the lung. The trial occurred between March 2018 and August 2022 at the 3rd Department of Medicine, Kapodistrian Medical School of Athens. The institutional review board of Sotiria Chest Diseases Hospital of Athens approved it. The trial adhered to Good Clinical Practice guidelines and the Declaration of Helsinki, and all patients or their legal representatives provided informed consent.

Patients:

The trial enrolled patients with metastatic LCNEC originating from the lung. Eligible patients had not received prior systemic treatment for LCNEC. Patients with brain metastases at diagnosis underwent Whole Brain Radiotherapy (WBRT) before starting systemic treatment.

Study Design:

The experimental group received a combination treatment regimen consisting of four cycles of Carboplatin, Etoposide, and Atezolizumab every 21 days.

Patients who achieved stable disease (SD) or a response (partial or complete) continued maintenance treatment with Atezolizumab until disease progression or discontinuation due to severe adverse events.

The control group received four cycles of Carboplatin and Etoposide. Immune checkpoint inhibitors were not allowed in later lines of treatment for the control group.

Response to therapy was assessed using CT scans and physical evaluations.

Endpoints:

Progression Free Survival (PFS): The time from treatment initiation to disease progression or death.

Overall Survival (OS): The time from treatment initiation to death. Overall Response Rate (ORR): The percentage of patients with a complete or partial response based on RECIST v1.1 criteria.

Duration of Response (DoR): The length of time the disease responded to treatment without progression on imaging studies.

Procedure:

Patients were treated at the 3rd Department of Medicine, Kapodistrian Medical School of Athens.

Approval for immunotherapy was obtained from the National Organisation for the Provision of Health Services (EOPYY) for each patient.

Blood samples for miR-375 and miR-21 analysis were collected at specific time points and processed according to standard procedures.

Analysis of miRNA expression was performed using the miRCURY LNA SYBR Green PCR Kit.

Statistical Analysis:

Rstudio was used for statistical analysis. The trial did not include a power analysis. The intention-to-treat principle was followed. Kaplan-Meier methods and Cox Regression survival analysis were used to estimate PFS and OS.

An analysis of the significance of the difference in characteristics between the experimental and control groups was conducted.

miR-21 and miR-375 Analysis:

Control samples for miR-21 and miR-375 were collected from volunteers without a cancer diagnosis, matching age with LCNEC patients.

Blood samples were collected at specific time points and processed to isolate plasma.

RNA was isolated from plasma samples, followed by cDNA synthesis and miRNA quantification using the miRCURY LNA SYBR Green PCR Kit.

MiR-103a-3p was used as a reference gene. Real-time PCR was performed to quantify miRNAs, and the results were expressed relative to the control group.

Eligibility criteria: Cohorts A and B:

Inclusion Criteria:

* Histologically confirmed Stage IV (metastatic) or unresectable locally advanced LCNEC
* No prior treatment
* With or without brain metastasis, if symptomatic patients should be treated with WBRT first
* Performance Status ≤ 2
* Life expectancy \> 3 months
* Written informed consent
* Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Exclusion Criteria:

* Prior treatment with chemotherapy, immunotherapy, targeted small molecule therapy, or radiation therapy (except WBRT for brain metastasis from LCNEC)
* Active or history of autoimmune disease or immune deficiency
* Treatment with systemic immunosuppressive medications with the following exceptions:

Patients who have received acute, low-dose systemic immunosuppressant medication (≤ 10 mg/day oral prednisone or equivalent) or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Medical Monitor approval has been obtained.

* Major surgical procedure other than for diagnosis within 4 weeks before initiation of study treatment, or anticipation of need for a major surgical procedure during the study
* Active malignancy or malignancy within 3 years
* Active tuberculosis
* Current severe, uncontrolled systemic disease other than cancer
* Known clinically significant liver disease
* Treatment with any other investigational agent or participation in another clinical study with therapeutic intent

Primary outcomes:
measure: Progression-free survival
timeFrame: Through study completion, an average of 3 years
measure: Overall survival
timeFrame: Through study completion, an average of 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Athens
country: Greece
facility: National and Kapodistrian University of Athens
city: Athens
country: Greece
facility: OCEBER
Study officials:
affiliation: National and Kapodistrian University of Athens
name: Konstantinos N Syrigos
role: STUDY_CHAIR
affiliation: National and Kapodistrian University of Athens
name: Georgios Evangelou
role: PRINCIPAL_INVESTIGATOR
affiliation: Konstantinos
name: Konstantinos N Syrigos
role: STUDY_DIRECTOR
References: