Clinical trial NCT05470595: A Single-arm Trial of Atezolizumab/Platinum/Etoposide for the Treatment of Advanced Large-cell Neuroendocrine Cancer of the Lung
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Large Cell Neuroendocrine Carcinoma of the Lung
Keywords: Lung Cancer
LCNEC
Neuroendocrine Carcinoma
Lead sponsor: Technische Universität Dresden
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2022-07-22
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall survival
timeFrame: appr. 72 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: appr. 72 months
measure: Immune Objective Response Rate (iORR)
timeFrame: appr. 72 months
measure: Disease Control Rate (DCR)
timeFrame: appr. 72 months
measure: Progression Free Survival (PFS)
timeFrame: appr. 72 months
measure: Immune Progression Free Survival (iPFS)
timeFrame: appr. 72 months
measure: Duration of Response (DoR)
timeFrame: appr. 72 months
measure: Progression Free Survival (PFS) rate at one year
timeFrame: 1 year
measure: Immune Progression Free Survival (iPFS) rate at one year
timeFrame: 1 year
measure: Overall survival at one year
timeFrame: 1 year
measure: Incidence, intensity, seriousness, relationship to Atezolizumab, and outcome of adverse events graded according to NCI CTCAE (v5.0).
timeFrame: appr. 72 months
Other outcomes:
measure: Secondary efficacy endpoints in defined molecular subtypes (NSCLC-type / SCLC-type)
timeFrame: appr. 72 months
measure: Quality of Life assessed by EORTC QLQ-C30.
timeFrame: appr. 72 months
measure: Quality of Life assessed by EORTC QLQ-LC13.
timeFrame: appr. 72 months
measure: Immune Effectors
timeFrame: appr. 72 months
measure: Mutational Landscape
timeFrame: appr. 72 months
measure: Tumor DNA (tDNA) level
timeFrame: appr. 72 months
measure: Therapy Resistance
timeFrame: appr. 72 months
Locations:
city: Berlin
country: Germany
facility: Charité - Universitätsklinikum Berlin Centrum 12, Medizinische Klinik
city: Berlin
country: Germany
facility: Evangelische Lungenklinik
city: Dresden
country: Germany
facility: Universitätsklinikum Dresden, Medizinische Klinik 1
city: Frankfurt am Main
country: Germany
facility: Klinikum der J.W. Goethe Universität, Medizinische Klinik II
city: Gauting
country: Germany
facility: Asklepios Fachkliniken München-Gauting
city: Großhansdorf
country: Germany
facility: LungenClinic Grosshansdorf GmbH
city: Halle (Saale)
country: Germany
facility: Krankenhaus St. Elisabeth und St. Barbara Halle (Saale) GmbH
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH, Universitätsklinikum Heidelberg
city: Hemer
country: Germany
facility: Lungenklinik Hemer des Deutschen Gemeinschafts-Diakonieverbandes GmbH
city: Immenhausen
country: Germany
facility: Lungenfachklinik Immenhausen
city: Köln
country: Germany
facility: Klinikum der Universität zu Köln, Klinik I für Innere Medizin
city: Mainz
country: Germany
facility: Klinikum der Johannes Gutenberg Universität, III. Med. Klinik und Poliklinik
city: Oldenburg
country: Germany
facility: Pius Hospital, Klinik für Hämatologie und Onkologie
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus GmbH
city: Winnenden
country: Germany
facility: Rems-Murr-Klinikum Winnenden, Klinik für Hämatologie, Onkologie und Palliativmedizin
Study officials:
affiliation: Technische Universität Dresden (TUD)
name: Martin Wermke, MD
role: PRINCIPAL_INVESTIGATOR
References: