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

Primary Purpose

Large Cell Neuroendocrine Carcinoma of the Lung

Status
Recruiting
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Atezolizumab
Sponsored by
Technische Universität Dresden
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Large Cell Neuroendocrine Carcinoma of the Lung focused on measuring Lung Cancer, LCNEC, Neuroendocrine Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Charité - Universitätsklinikum Berlin Centrum 12, Medizinische Klinik
  • Evangelische LungenklinikRecruiting
  • Universitätsklinikum Dresden, Medizinische Klinik 1Recruiting
  • Klinikum der J.W. Goethe Universität, Medizinische Klinik II
  • Asklepios Fachkliniken München-GautingRecruiting
  • LungenClinic Grosshansdorf GmbHRecruiting
  • Thoraxklinik Heidelberg gGmbH, Universitätsklinikum Heidelberg
  • Lungenklinik Hemer des Deutschen Gemeinschafts-Diakonieverbandes GmbH
  • Lungenfachklinik ImmenhausenRecruiting
  • Klinikum der Universität zu Köln, Klinik I für Innere Medizin
  • Klinikum der Johannes Gutenberg Universität, III. Med. Klinik und Poliklinik
  • Pius Hospital, Klinik für Hämatologie und OnkologieRecruiting
  • Rems-Murr-Klinikum Winnenden, Klinik für Hämatologie, Onkologie und Palliativmedizin
  • Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Atezolizumab/Platinum/Etoposide

Arm Description

Atezolizumab/Platinum/Etoposide Platinum will be cisplatin or carboplatin at the investigators discretion.

Outcomes

Primary Outcome Measures

Overall survival
To assess the efficacy of Atezolizumab in addition to standard of care chemotherapy (Platinum/Etoposide) in LCNEC as measured by overall survival.

Secondary Outcome Measures

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

Full Information

First Posted
July 13, 2022
Last Updated
July 20, 2022
Sponsor
Technische Universität Dresden
Collaborators
Roche Pharma AG
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1. Study Identification

Unique Protocol Identification Number
NCT05470595
Brief Title
A Single-arm Trial of Atezolizumab/Platinum/Etoposide for the Treatment of Advanced Large-cell Neuroendocrine Cancer of the Lung
Acronym
LCNEC-ALPINE
Official Title
A Phase II, Single-arm Trial of Atezolizumab/Platinum/Etoposide for the Treatment of Advanced Large-cell Neuroendocrine Cancer of the Lung
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 18, 2022 (Actual)
Primary Completion Date
January 31, 2028 (Anticipated)
Study Completion Date
January 31, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Technische Universität Dresden
Collaborators
Roche Pharma AG

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Large Cell Neuroendocrine Carcinoma of the Lung
Keywords
Lung Cancer, LCNEC, Neuroendocrine Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
67 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Atezolizumab/Platinum/Etoposide
Arm Type
Experimental
Arm Description
Atezolizumab/Platinum/Etoposide Platinum will be cisplatin or carboplatin at the investigators discretion.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall survival
Description
To assess the efficacy of Atezolizumab in addition to standard of care chemotherapy (Platinum/Etoposide) in LCNEC as measured by overall survival.
Time Frame
appr. 72 months
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
According to RECIST v1.1 as assessed by local investigator.
Time Frame
appr. 72 months
Title
Immune Objective Response Rate (iORR)
Description
According to iRECIST as assessed by local investigator.
Time Frame
appr. 72 months
Title
Disease Control Rate (DCR)
Description
According to RECIST v1.1 as assessed by local investigator.
Time Frame
appr. 72 months
Title
Progression Free Survival (PFS)
Time Frame
appr. 72 months
Title
Immune Progression Free Survival (iPFS)
Time Frame
appr. 72 months
Title
Duration of Response (DoR)
Time Frame
appr. 72 months
Title
Progression Free Survival (PFS) rate at one year
Time Frame
1 year
Title
Immune Progression Free Survival (iPFS) rate at one year
Time Frame
1 year
Title
Overall survival at one year
Time Frame
1 year
Title
Incidence, intensity, seriousness, relationship to Atezolizumab, and outcome of adverse events graded according to NCI CTCAE (v5.0).
Time Frame
appr. 72 months
Other Pre-specified Outcome Measures:
Title
Secondary efficacy endpoints in defined molecular subtypes (NSCLC-type / SCLC-type)
Time Frame
appr. 72 months
Title
Quality of Life assessed by EORTC QLQ-C30.
Time Frame
appr. 72 months
Title
Quality of Life assessed by EORTC QLQ-LC13.
Time Frame
appr. 72 months
Title
Immune Effectors
Description
Changes in cellular and humoral immune effectors in peripheral blood and their correlation with response.
Time Frame
appr. 72 months
Title
Mutational Landscape
Description
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.
Time Frame
appr. 72 months
Title
Tumor DNA (tDNA) level
Description
Dynamics of circulating tumor DNA levels (changes from baseline).
Time Frame
appr. 72 months
Title
Therapy Resistance
Description
Mechanisms of therapy resistance (changes of immune invasion and mutational landscape in tumor re-biopsy upon progression).
Time Frame
appr. 72 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent 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%) 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) Planned treatment with Carboplatin or Cisplatin and Etoposide (SoC) ECOG performance status: 0-2 age ≥18 years measurable disease according to RECIST v1.1 adequate organ function defined as: ALAT/ASAT ≤2.5x ULN or ≤3.5x ULN in case of liver metastases Bilirubin ≤1.5x ULN or ≤2.5x ULN in case of liver metastases Creatinine ≤1.5x ULN or Creatinine clearance according to Cockroft-Gault >60 ml/min Neutrophils ≥1 Gpt/l, Platelets >50 Gpt/l unless caused by bone marrow carcinosis Exclusion Criteria: Symptomatic brain metastases (patients with asymptomatic brain metastases are allowed provided they are stable without steroid treatment for at least 3 weeks) Severe autoimmune disease (patients with endocrine autoimmune disorders are allowed as long as they are on stable substitution treatment) Severe uncontrolled infection Prior treatment with either Atezolizumab or other immune checkpoint inhibitor Any prior treatment for metastatic disease
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Martin Wermke, MD
Phone
+49 351 7566
Email
martin.wermke@ukdd.de
First Name & Middle Initial & Last Name or Official Title & Degree
Felix C Saalfeld, MD
Email
felix.saalfeld@ukdd.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martin Wermke, MD
Organizational Affiliation
Technische Universität Dresden (TUD)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Charité - Universitätsklinikum Berlin Centrum 12, Medizinische Klinik
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nikolaj Frost, MD
Facility Name
Evangelische Lungenklinik
City
Berlin
ZIP/Postal Code
12125
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Grohé, Prof. Dr.
Facility Name
Universitätsklinikum Dresden, Medizinische Klinik 1
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Wermke, MD
Facility Name
Klinikum der J.W. Goethe Universität, Medizinische Klinik II
City
Frankfurt am Main
ZIP/Postal Code
60590
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jan Alexander Stratmann, MD
Facility Name
Asklepios Fachkliniken München-Gauting
City
Gauting
ZIP/Postal Code
82131
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Niels Reinmuth, MD
Facility Name
LungenClinic Grosshansdorf GmbH
City
Großhansdorf
ZIP/Postal Code
22927
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Reck, MD
Facility Name
Thoraxklinik Heidelberg gGmbH, Universitätsklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69126
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Farastuk Bozorgmehr, MD
Facility Name
Lungenklinik Hemer des Deutschen Gemeinschafts-Diakonieverbandes GmbH
City
Hemer
ZIP/Postal Code
58675
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Monika Serke, MD
Facility Name
Lungenfachklinik Immenhausen
City
Immenhausen
ZIP/Postal Code
34376
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Achim Rittmeyer, MD
Facility Name
Klinikum der Universität zu Köln, Klinik I für Innere Medizin
City
Köln
ZIP/Postal Code
50937
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jürgen Wolf, MD
Facility Name
Klinikum der Johannes Gutenberg Universität, III. Med. Klinik und Poliklinik
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jürgen Alt, MD
Facility Name
Pius Hospital, Klinik für Hämatologie und Onkologie
City
Oldenburg
ZIP/Postal Code
26121
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frank Griesinger, MD
Facility Name
Rems-Murr-Klinikum Winnenden, Klinik für Hämatologie, Onkologie und Palliativmedizin
City
Winnenden
ZIP/Postal Code
71364
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Netchaeva
Facility Name
Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken
City
Würzburg
ZIP/Postal Code
97078
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pius Jung, MD

12. IPD Sharing Statement

Learn more about this trial

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

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