Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Carcinoma

Carcinoma, Neuroendocrine

Lung Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Adenocarcinoma

Neoplasms, Nerve Tissue

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Carboplatin

Etoposide

Cisplatin

Etoposide phosphate

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Pembrolizumab 200mg IV day 1 with Carboplatin AUC 6 IV day 1 or Cisplatin 80mg/m2 day 1 with etoposide 100mg/m2 days 1-3 of 21 day cycle. Repeat 4-6 cycles to be followed by maintenance Pembrolizumab 200mg IV day 1 every 21 days until progression or intolerance for up to 2 years.

Intravenous administration of pembrolizumab in combination with cisplatin or carboplatin and etoposide in first line metastatic or unresectable high grade neuroendocrine carcinoma:

Robert Ramirez, DO

The purpose of this study is to test the efficacy, safety, and tolerability of the combination of chemotherapy treatment, which could be either Cisplatin or carboplatin and etoposide, and the research study drug, Pembrolizumab (also known as MK-3475) in patients with high grade neuroendocrine carcinomas of the gastroenteropancreatic system or lung who are chemotherapy naïve. The chemotherapy treatment you receive will be either Cisplatin or carboplatin and etoposide. the participant's doctor will discuss this choice with you and determined which chemotherapy treatment is best for you.

Combination chemotherapy is the mainstay of treatment for patients with high grade GEPNETs and neuroendocrine carcinomas of the lung.

This study will utilize pembrolizumab, a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor, thus blocks a protective mechanism of cancer cells and thereby allows the immune system to destroy them, in combination with chemotherapy.

Combination chemotherapy and pembrolizumab was recently FDA approved and ongoing trials are utilizing this or similar combination with preliminary data demonstrating a promising safety profile.

Pembrolizumab With Chemotherapy in Metastatic or Unresectable High Grade Gastroenteropancreatic or Lung Neuroendocrine Carcinoma

A Phase II Trial of Pembrolizumab in Combination With Cisplatin or Carboplatin and Etoposide in Chemotherapy naïve Patients With Metastatic or Unresectable High Grade Gastroenteropancreatic or Lung (Excluding Small Cell) Neuroendocrine Carcinoma

Assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Merck Sharp & Dohme LLC

Ochsner Health System

Principal Investigator

Hematinics

Immunomodulating Agents

Atezolizumab

Iron-Dextran Complex

Enzyme Inhibitors

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

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

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

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

Konstantinos N Syrigos

Georgios Evangelou

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.

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.

Atezolizumab in Large Cell Neuroendocrine Carcinoma

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

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

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

Oncology Center of Biochemical Education And Research

Small Cell Lung Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

DLL3-Directed Chimeric Antigen Receptor T-cells (CAR T)

DLL3 directed autologous Chimeric Antigen Receptor T-cells

LB2102

Legend Biotech USA

Tina Swartzlander

Alberto Chiappori, MD

Zhonglin Hao, MD

Heather L Heath

Hope Wei, BA

Jordan Weiss, BA

Jacob Sands, MD

Adam Schoenfeld, MD

Sophie Hieronymi

This is a phase 1, first-in-human, open-label, multicenter, dose escalation and expansion study of DLL3-targeted chimeric antigen receptor T-cells in subjects with extensive stage small cell lung cancer or large cell neuroendocrine lung cancer.

This is a phase 1, first-in-human, open-label, multicenter, dose escalation and expansion study of DLL3-targeted chimeric antigen receptor T-cells in subjects with extensive stage small cell lung cancer or large cell neuroendocrine lung cancer. The study comprises a dose-escalation component (Part A) and a cohort expansion component (Part B). Up to 41 subjects will be treated in this study. Part A will enroll and treat up to 24 subjects and Part B will be conducted after the recommended dose for expansion (RDE) has been identified in Part A and enroll up to 17 subjects. Both parts of this trial will include a Screening Period, a Pretreatment Period, a Treatment Period, a Follow-Up Period, and a Post-Progression Follow-Up Period.

DLL3-Directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer

A First in Human Dose Escalation and Cohort Expansion Study of DLL3-directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer

Multiple doses will be tested to establish a recommended dose

Treatment of additional patients at the recommended dose as identified in the initial dose escalation part of the study

Measured by Response Evaluation Criteria In Solid Tumors (RECIST)

CAR-positive T cell counts in cells/microliter (μL) blood

Number of subjects with presence of anti-LB2102 antibodies

Legend Biotech USA Inc

Carcinoma, Small Cell

* Subjects will receive Abemaciclib (200 mg), orally every 12 hours on days 1 to 28 of a 28-day cycle for a total of 56 doses per cycle.
* Subjects will be evaluated after 4 weeks (1st cycle) and then every 8 weeks (2 cycles) with radiographic imaging to assess response to treatment.

Abemaciclib (CDK4/6 inhibitors) is an investigational drug that works by interrupting the rapid and uncontrolled growth of cancer cells. Some cancer cells develop because their cells overrun the molecular brakes that normally permit cell to divide only when they are needed to replace old ones. These brakes are regulated by a group of enzymes known as cyclin-dependent kinases (CDKs). Alterations causing over-activity of two of these enzymes, CDK4 andCDK6, are found in a variety of cancers, including small cell lung cancer with retinoblastoma (Rb) protein.The drugs work by selectively turning off the overactive CDK4 and CDK6. As a result, the cancer cells' division cycle is halted, preventing them from proliferating.

Abemaciclib,

Afshin Dowlati, MD

The purpose of this study is to:

* Test how well the study medicine Abemaciclib, a CDK4/6 inhibitor, works to shrink lung cancer tumors in the body.
* Test the safety of Abemaciclib when given to participants with small cell lung cancer (SCLC), large cell neuroendocrine lung cancer, extrapulmonary small cell cancers and other high grade neuroendocrine cancers of the lung. Specifically, this study is looking at SCLC, large cell neuroendocrine lung cancer, extrapulmonary small cell cancers and other high grade neuroendocrine cancers of the lung that have not responded to treatment (refractory) or come back after treatment with chemotherapy (relapsed) as the study medication has been shown to be effective any time the disease relapses not just in the first few months.

This is a multicenter, non-randomized, phase 2, single arm study to determine the efficacy and safety of Abemaciclib as a single agent in patients with biopsy-proven wild type Rb extensive stage of SCLC, with platinum refractory disease (defined as no response after 1-2 cycles of chemotherapy or relapse defined as initial response but relapse after completing platinum-based chemotherapy). Subjects with other tumor types with biopsy proven wild type Rb such as large cell neuroendocrine lung cancer, extrapulmonary small cell cancers and other high grade neuroendocrine cancers of the lung may also be enrolled.

Abemaciclib (CDK4/6 inhibitors) is an investigational drug that works by interrupting the rapid and uncontrolled growth of cancer cells. Some cancer cells develop because their cells overrun the molecular brakes that normally permit cell to divide only when they are needed to replace old ones. These brakes are regulated by a group of enzymes known as cyclin-dependent kinases (CDKs). Alterations causing over-activity of two of these enzymes, CDK4 and CDK6, are found in a variety of cancers, including small cell lung cancer with retinoblastoma (Rb) protein. The drugs work by selectively turning off the overactive CDK4 and CDK6. As a result, the cancer cells' division cycle is halted, preventing them from proliferating.

The objectives of this study include determining:

* Overall Response Rate (ORR) after the first cycle (4 weeks) and then every 8 weeks.
* Progression Free Survival (PFS)assessed at 6 months and Overall Survival (OS).
* Safety and adverse events
* Duration of response in all responders

Targeted Therapy With CDK4/6 Inhibitors in Chemo-Refractory, Rb Wild-Type Extensive SCLC

Targeted Therapy With CDK4/6 Inhibitors in Chemo- Refractory/Relapsed, Rb Wild-type Extensive Small Cell Lung Cancer (SCLC), Large Cell Neuroendocrine Lung Cancer, Extrapulmonary Small Cell Cancers and Other High Grade Neuroendocrine Cancers of the Lung, an Open Label Phase 2 Trial.

Individual participant data that underlie or influence the results observed from the study.

Overall Response Rate (ORR) defined as the proportion of subjects in the analysis population who have complete response (CR) or partial response (PR) using RECIST 1.1 criteria at any time during the study. Response for the primary analyses will be determined by independent radiology review.

CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.

PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Defined as the time from allocation to the first documented disease progression according to RECIST 1.1 or death due to any cause, whichever occurs first.

Overall Survival (OS) defined as the time from start of study to death due to any cause.

Safety and adverse events (AE's) (CTCAE grade version 5.0) will be assessed by quantifying the toxicities and grades experienced by subjects who have received Abemaciclib (Verzenio®\[LY2835219\]) including serious adverse events (SAEs). All SE's and grade 3 and 4 AE's will be tabulated.

Duration of response in all responders (DoR using RECIST 1.1) assessed from the time that measurement criteria met until progressive disease is objectively documented.

Progressive disease defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pembrolizumab With Chemotherapy in Metastatic or Unresectable High Grade Gastroenteropancreatic or Lung Neuroendocrine Carcinoma	NCT03901378	Neuroendocrine ... Large Cell Neur... High Grade Neur...	Pembrolizumab	18 Years -	Ochsner Health System
Atezolizumab in Large Cell Neuroendocrine Carcinoma	NCT06049966	Large Cell Neur...	Atezolizumab Carboplatin Etoposide	18 Years - 90 Years	Oncology Center of Biochemical Education And Research
DLL3-Directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer	NCT05680922	Small Cell Lung... Large Cell Neur...	LB2102	18 Years -	Legend Biotech USA Inc
Targeted Therapy With CDK4/6 Inhibitors in Chemo-Refractory, Rb Wild-Type Extensive SCLC	NCT04010357	Small-cell Lung... Large Cell Neur... Extrapulmonary ...	Abemaciclib,	19 Years -	Case Comprehensive Cancer Center
DLL3-Directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer	NCT05680922	Small Cell Lung... Large Cell Neur...	LB2102	18 Years -	Legend Biotech USA Inc
DLL3-Directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer	NCT05680922	Small Cell Lung... Large Cell Neur...	LB2102	18 Years -	Legend Biotech USA Inc
Targeted Therapy With CDK4/6 Inhibitors in Chemo-Refractory, Rb Wild-Type Extensive SCLC	NCT04010357	Small-cell Lung... Large Cell Neur... Extrapulmonary ...	Abemaciclib,	19 Years -	Case Comprehensive Cancer Center

Spots Global Cancer Trial Database for large cell neuroendocrine carcinoma of the lung