Atezolizumab in Large Cell Neuroendocrine Carcinoma

NCT ID: NCT06049966

Last Updated: 2023-09-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-01
• Study Completion Date: 2023-05-01

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.

Conditions

Large Cell Neuroendocrine Carcinoma of the Lung

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

Carboplatin 5 AUC D1 plus Etoposide 100mg/m2 D1-D3 plus Atezolizumab 1200 mg, Q21, 4 Cycles and then maintenance Atezolizumab 1200 mg Q21

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

TECENTRIQ C/S.SOL.IN 1200MG/VIAL (20ML) 1 VIAL x 20ML

Carboplatin

Intervention Type: DRUG

SOL.INF 450MG/45ML VIAL ΒΤx1VIALx45ML

Etoposide

Intervention Type: DRUG

ETOPOSIDE/PHARMACHEMIE SOL.INF 100MG/5ML VIAL BT x 10 VIALS x 5 ML

Arm B

Carboplatin 5 AUC D1 plus Etoposide 100mg/m2 D1-D3, 4 Cycles and then observation

Group Type: ACTIVE_COMPARATOR

Carboplatin

Intervention Type: DRUG

SOL.INF 450MG/45ML VIAL ΒΤx1VIALx45ML

Etoposide

Intervention Type: DRUG

ETOPOSIDE/PHARMACHEMIE SOL.INF 100MG/5ML VIAL BT x 10 VIALS x 5 ML

Interventions

Atezolizumab

TECENTRIQ C/S.SOL.IN 1200MG/VIAL (20ML) 1 VIAL x 20ML

Intervention Type: DRUG

Carboplatin

SOL.INF 450MG/45ML VIAL ΒΤx1VIALx45ML

Intervention Type: DRUG

Etoposide

ETOPOSIDE/PHARMACHEMIE SOL.INF 100MG/5ML VIAL BT x 10 VIALS x 5 ML

Intervention Type: DRUG

Other Intervention Names

Tecentriq; CARBOPLATIN/HOSPIRA

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Oncology Center of Biochemical Education And Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Konstantinos N Syrigos

Role: STUDY_CHAIR

National and Kapodistrian University of Athens

Georgios Evangelou

Role: PRINCIPAL_INVESTIGATOR

National and Kapodistrian University of Athens

Konstantinos N Syrigos

Role: STUDY_DIRECTOR

Konstantinos

Locations

National and Kapodistrian University of Athens

Athens, , Greece

OCEBER

Athens, , Greece

Countries

Greece

Other Identifiers

UPI-2023-2304

Identifier Type: -

Identifier Source: org_study_id