A Single-arm Trial of Atezolizumab/Platinum/Etoposide for the Treatment of Advanced Large-cell Neuroendocrine Cancer of the Lung (LCNEC-ALPINE)

A Phase II, Single-arm Trial of Atezolizumab/Platinum/Etoposide for the Treatment of Advanced Large-cell Neuroendocrine Cancer of the Lung

This phase II clinical trial evaluates the efficacy, safety and tolerability of Atezolizumab in addition to standard of care chemotherapy (Platinum/Etoposide) in LCNEC.

Study Overview

• Status: Recruiting
• Conditions: Large Cell Neuroendocrine Carcinoma of the Lung
• Intervention / Treatment: Drug: Atezolizumab

• Study Type: Interventional
• Enrollment (Estimated): 67
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Martin Wermke, MD; Phone Number: +49 351 7566; Email: martin.wermke@ukdd.de
• Study Contact Backup: Name: Felix C Saalfeld, MD; Email: felix.saalfeld@ukdd.de

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Not yet recruiting
    • Charité - Universitätsklinikum Berlin Centrum 12, Medizinische Klinik
    • Contact: Nikolaj Frost, MD
  • Berlin, Germany, 12125
    • Recruiting
    • Evangelische Lungenklinik
    • Contact: Christian Grohé, Prof. Dr.
  • Dresden, Germany, 01307
    • Recruiting
    • Universitätsklinikum Dresden, Medizinische Klinik 1
    • Contact: Martin Wermke, MD
  • Frankfurt am Main, Germany, 60590
    • Not yet recruiting
    • Klinikum der J.W. Goethe Universität, Medizinische Klinik II
    • Contact: Jan Alexander Stratmann, MD
  • Gauting, Germany, 82131
    • Recruiting
    • Asklepios Fachkliniken München-Gauting
    • Contact: Niels Reinmuth, MD
  • Großhansdorf, Germany, 22927
    • Recruiting
    • LungenClinic Grosshansdorf GmbH
    • Contact: Martin Reck, MD
  • Heidelberg, Germany, 69126
    • Not yet recruiting
    • Thoraxklinik Heidelberg gGmbH, Universitätsklinikum Heidelberg
    • Contact: Farastuk Bozorgmehr, MD
  • Hemer, Germany, 58675
    • Not yet recruiting
    • Lungenklinik Hemer des Deutschen Gemeinschafts-Diakonieverbandes GmbH
    • Contact: Monika Serke, MD
  • Immenhausen, Germany, 34376
    • Recruiting
    • Lungenfachklinik Immenhausen
    • Contact: Achim Rittmeyer, MD
  • Köln, Germany, 50937
    • Not yet recruiting
    • Klinikum der Universität zu Köln, Klinik I für Innere Medizin
    • Contact: Jürgen Wolf, MD
  • Mainz, Germany, 55131
    • Not yet recruiting
    • Klinikum der Johannes Gutenberg Universität, III. Med. Klinik und Poliklinik
    • Contact: Jürgen Alt, MD
  • Oldenburg, Germany, 26121
    • Recruiting
    • Pius Hospital, Klinik für Hämatologie und Onkologie
    • Contact: Frank Griesinger, MD
  • Winnenden, Germany, 71364
    • Not yet recruiting
    • Rems-Murr-Klinikum Winnenden, Klinik für Hämatologie, Onkologie und Palliativmedizin
    • Contact: Maria Netchaeva
  • Würzburg, Germany, 97078
    • Not yet recruiting
    • Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken
    • Contact: Pius Jung, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent
2. Patients with locally advanced or metastatic large-cell neuroendocrine carcinoma of the lung (LCNEC) without curative treatment options (patients with mixed histology are eligible if LCNEC is the predominant histology i.e. ≥50%)
3. Previously untreated with systemic therapy (note: patients relapsing after curative radio chemotherapy or adjuvant chemotherapy are eligible if relapse occurs ≥6 months after discontinuation of curative treatment)
4. Planned treatment with Carboplatin or Cisplatin and Etoposide (SoC)
5. ECOG performance status: 0-2
6. age ≥18 years
7. measurable disease according to RECIST v1.1

8. adequate organ function defined as:

   1. ALAT/ASAT ≤2.5x ULN or ≤3.5x ULN in case of liver metastases
   2. Bilirubin ≤1.5x ULN or ≤2.5x ULN in case of liver metastases
   3. Creatinine ≤1.5x ULN or Creatinine clearance according to Cockroft-Gault >60 ml/min
   4. Neutrophils ≥1 Gpt/l, Platelets >50 Gpt/l unless caused by bone marrow carcinosis

Exclusion Criteria:

1. Symptomatic brain metastases (patients with asymptomatic brain metastases are allowed provided they are stable without steroid treatment for at least 3 weeks)
2. Severe autoimmune disease (patients with endocrine autoimmune disorders are allowed as long as they are on stable substitution treatment)
3. Severe uncontrolled infection
4. Prior treatment with either Atezolizumab or other immune checkpoint inhibitor
5. Any prior treatment for metastatic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atezolizumab/Platinum/Etoposide; Atezolizumab/Platinum/Etoposide Platinum will be cisplatin or carboplatin at the investigators discretion.	Drug: Atezolizumab; Atezolizumab (IMP) will be added to Platinum/Etoposide (Standard-of-Care). Four cycles of combined immunochemotherapy 3qw will be follows by maintenance with atezolizumab monotherapy until progression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	To assess the efficacy of Atezolizumab in addition to standard of care chemotherapy (Platinum/Etoposide) in LCNEC as measured by overall survival.	appr. 72 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	According to RECIST v1.1 as assessed by local investigator.	appr. 72 months
Immune Objective Response Rate (iORR)	According to iRECIST as assessed by local investigator.	appr. 72 months
Disease Control Rate (DCR)	According to RECIST v1.1 as assessed by local investigator.	appr. 72 months
Progression Free Survival (PFS)		appr. 72 months
Immune Progression Free Survival (iPFS)		appr. 72 months
Duration of Response (DoR)		appr. 72 months
Progression Free Survival (PFS) rate at one year		1 year
Immune Progression Free Survival (iPFS) rate at one year		1 year
Overall survival at one year		1 year
Incidence, intensity, seriousness, relationship to Atezolizumab, and outcome of adverse events graded according to NCI CTCAE (v5.0).		appr. 72 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary efficacy endpoints in defined molecular subtypes (NSCLC-type / SCLC-type)		appr. 72 months
Quality of Life assessed by EORTC QLQ-C30.		appr. 72 months
Quality of Life assessed by EORTC QLQ-LC13.		appr. 72 months
Immune Effectors	Changes in cellular and humoral immune effectors in peripheral blood and their correlation with response.	appr. 72 months
Mutational Landscape	Mutational landscape of LCNEC in comparison to SCLC as well as squamous and Adenocarcinoma of the lung. The analysis will be using whole genome sequencing.	appr. 72 months
Tumor DNA (tDNA) level	Dynamics of circulating tumor DNA levels (changes from baseline).	appr. 72 months
Therapy Resistance	Mechanisms of therapy resistance (changes of immune invasion and mutational landscape in tumor re-biopsy upon progression).	appr. 72 months

Collaborators and Investigators

• Sponsor: Technische Universität Dresden
• Collaborators: Roche Pharma AG
• Investigators: Principal Investigator: Martin Wermke, MD, Technische Universität Dresden (TUD)

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2022
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2029

Study Registration Dates

• First Submitted: July 13, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (Actual): July 22, 2022

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Lung Cancer; Neuroendocrine Carcinoma; LCNEC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Lung Neoplasms; Carcinoma, Neuroendocrine; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Atezolizumab
• Other Study ID Numbers: TUD-ALPINE-077; 2020-002683-31 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No