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

Large Cell Neuroendocrine Carcinoma of the Lung Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05470595
• Other study ID #: TUD-ALPINE-077
• Secondary ID: 2020-002683-31
• Status: Recruiting
• Phase: Phase 2
• Start date: January 18, 2022
• Est. completion date: January 31, 2029

Study information

• Verified date: November 2023
• Source: Technische Universität Dresden
• Contact: Martin Wermke, MD
• Phone: +49 351 7566
• Email: martin.wermke[@]ukdd.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 67
• Est. completion date: January 31, 2029
• Est. primary completion date: January 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Neuroendocrine
• Large Cell Neuroendocrine Carcinoma of the Lung
• Lung Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Germany	Charité - Universitätsklinikum Berlin Centrum 12, Medizinische Klinik	Berlin
Germany	Evangelische Lungenklinik	Berlin
Germany	Universitätsklinikum Dresden, Medizinische Klinik 1	Dresden
Germany	Klinikum der J.W. Goethe Universität, Medizinische Klinik II	Frankfurt am Main
Germany	Asklepios Fachkliniken München-Gauting	Gauting
Germany	LungenClinic Grosshansdorf GmbH	Großhansdorf
Germany	Thoraxklinik Heidelberg gGmbH, Universitätsklinikum Heidelberg	Heidelberg
Germany	Lungenklinik Hemer des Deutschen Gemeinschafts-Diakonieverbandes GmbH	Hemer
Germany	Lungenfachklinik Immenhausen	Immenhausen
Germany	Klinikum der Universität zu Köln, Klinik I für Innere Medizin	Köln
Germany	Klinikum der Johannes Gutenberg Universität, III. Med. Klinik und Poliklinik	Mainz
Germany	Pius Hospital, Klinik für Hämatologie und Onkologie	Oldenburg
Germany	Rems-Murr-Klinikum Winnenden, Klinik für Hämatologie, Onkologie und Palliativmedizin	Winnenden
Germany	Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken	Würzburg

Sponsors (2)

Lead Sponsor	Collaborator
Technische Universität Dresden	Roche Pharma AG

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Secondary efficacy endpoints in defined molecular subtypes (NSCLC-type / SCLC-type)		appr. 72 months
Other	Quality of Life assessed by EORTC QLQ-C30.		appr. 72 months
Other	Quality of Life assessed by EORTC QLQ-LC13.		appr. 72 months
Other	Immune Effectors	Changes in cellular and humoral immune effectors in peripheral blood and their correlation with response.	appr. 72 months
Other	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
Other	Tumor DNA (tDNA) level	Dynamics of circulating tumor DNA levels (changes from baseline).	appr. 72 months
Other	Therapy Resistance	Mechanisms of therapy resistance (changes of immune invasion and mutational landscape in tumor re-biopsy upon progression).	appr. 72 months
Primary	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	Objective Response Rate (ORR)	According to RECIST v1.1 as assessed by local investigator.	appr. 72 months
Secondary	Immune Objective Response Rate (iORR)	According to iRECIST as assessed by local investigator.	appr. 72 months
Secondary	Disease Control Rate (DCR)	According to RECIST v1.1 as assessed by local investigator.	appr. 72 months
Secondary	Progression Free Survival (PFS)		appr. 72 months
Secondary	Immune Progression Free Survival (iPFS)		appr. 72 months
Secondary	Duration of Response (DoR)		appr. 72 months
Secondary	Progression Free Survival (PFS) rate at one year		1 year
Secondary	Immune Progression Free Survival (iPFS) rate at one year		1 year
Secondary	Overall survival at one year		1 year
Secondary	Incidence, intensity, seriousness, relationship to Atezolizumab, and outcome of adverse events graded according to NCI CTCAE (v5.0).		appr. 72 months