Atezolizumab in Large Cell Neuroendocrine Carcinoma (LANCE)

September 16, 2023 updated by: Oncology Center of Biochemical Education And Research

Effectiveness of Atezolizumab in Large Cell Neuroendocrine Carcinoma of the Lung and the Value of miR21 and miR-375 as Biomarkers

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Greece
      • Athens, Greece, 11527
        • National and Kapodistrian University of Athens
      • Athens, Greece, 11527
        • OCEBER

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Drug: Atezolizumab
TECENTRIQ C/S.SOL.IN 1200MG/VIAL (20ML) 1 VIAL x 20ML
Other Names:
  • Tecentriq
Drug: Carboplatin
SOL.INF 450MG/45ML VIAL ΒΤx1VIALx45ML
Other Names:
  • CARBOPLATIN/HOSPIRA
Drug: Etoposide
ETOPOSIDE/PHARMACHEMIE SOL.INF 100MG/5ML VIAL BT x 10 VIALS x 5 ML
Active Comparator: Arm B
Carboplatin 5 AUC D1 plus Etoposide 100mg/m2 D1-D3, 4 Cycles and then observation
Drug: Carboplatin
SOL.INF 450MG/45ML VIAL ΒΤx1VIALx45ML
Other Names:
  • CARBOPLATIN/HOSPIRA
Drug: Etoposide
ETOPOSIDE/PHARMACHEMIE SOL.INF 100MG/5ML VIAL BT x 10 VIALS x 5 ML

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: Through study completion, an average of 3 years
Progression Free Survival (PFS) was defined as the time from treatment initiation to disease progression οr death. Patients alive without progression at the last follow-up were censored at the date of the deadline for follow-up
Through study completion, an average of 3 years
Overall survival
Time Frame: Through study completion, an average of 3 years
Overall survival (OS) was defined as the time from treatment initiation to death, and patients alive during the last follow-up were censored at the date of the deadline for follow-up
Through study completion, an average of 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oncology Center of Biochemical Education And Research

Investigators

  • Study Chair: Konstantinos N Syrigos, National and Kapodistrian University of Athens
  • Principal Investigator: Georgios Evangelou, National and Kapodistrian University of Athens
  • Study Director: Konstantinos N Syrigos, Konstantinos

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2018

Primary Completion (Actual)

August 1, 2022

Study Completion (Actual)

May 1, 2023

Study Registration Dates

First Submitted

September 10, 2023

First Submitted That Met QC Criteria

September 16, 2023

First Posted (Actual)

September 22, 2023

Study Record Updates

Last Update Posted (Actual)

September 22, 2023

Last Update Submitted That Met QC Criteria

September 16, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UPI-2023-2304

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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