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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)

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ClinicalTrials.gov Identifier: NCT05470595
Recruitment Status : Recruiting
First Posted : July 22, 2022
Last Update Posted : November 2, 2023
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Technische Universität Dresden

Tracking Information
First Submitted Date  ICMJE July 13, 2022
First Posted Date  ICMJE July 22, 2022
Last Update Posted Date November 2, 2023
Actual Study Start Date  ICMJE January 18, 2022
Estimated Primary Completion Date January 31, 2028   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 20, 2022)		 Overall survival [ Time Frame: appr. 72 months ]
To assess the efficacy of Atezolizumab in addition to standard of care chemotherapy (Platinum/Etoposide) in LCNEC as measured by overall survival.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2022)
  • Objective Response Rate (ORR) [ Time Frame: appr. 72 months ]
    According to RECIST v1.1 as assessed by local investigator.
  • Immune Objective Response Rate (iORR) [ Time Frame: appr. 72 months ]
    According to iRECIST as assessed by local investigator.
  • Disease Control Rate (DCR) [ Time Frame: appr. 72 months ]
    According to RECIST v1.1 as assessed by local investigator.
  • Progression Free Survival (PFS) [ Time Frame: appr. 72 months ]
  • Immune Progression Free Survival (iPFS) [ Time Frame: appr. 72 months ]
  • Duration of Response (DoR) [ Time Frame: appr. 72 months ]
  • Progression Free Survival (PFS) rate at one year [ Time Frame: 1 year ]
  • Immune Progression Free Survival (iPFS) rate at one year [ Time Frame: 1 year ]
  • Overall survival at one year [ Time Frame: 1 year ]
  • Incidence, intensity, seriousness, relationship to Atezolizumab, and outcome of adverse events graded according to NCI CTCAE (v5.0). [ Time Frame: appr. 72 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 20, 2022)
  • Secondary efficacy endpoints in defined molecular subtypes (NSCLC-type / SCLC-type) [ Time Frame: appr. 72 months ]
  • Quality of Life assessed by EORTC QLQ-C30. [ Time Frame: appr. 72 months ]
  • Quality of Life assessed by EORTC QLQ-LC13. [ Time Frame: appr. 72 months ]
  • Immune Effectors [ Time Frame: appr. 72 months ]
    Changes in cellular and humoral immune effectors in peripheral blood and their correlation with response.
  • Mutational Landscape [ Time Frame: appr. 72 months ]
    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.
  • Tumor DNA (tDNA) level [ Time Frame: appr. 72 months ]
    Dynamics of circulating tumor DNA levels (changes from baseline).
  • Therapy Resistance [ Time Frame: appr. 72 months ]
    Mechanisms of therapy resistance (changes of immune invasion and mutational landscape in tumor re-biopsy upon progression).
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Single-arm Trial of Atezolizumab/Platinum/Etoposide for the Treatment of Advanced Large-cell Neuroendocrine Cancer of the Lung
Official Title  ICMJE A Phase II, Single-arm Trial of Atezolizumab/Platinum/Etoposide for the Treatment of Advanced Large-cell Neuroendocrine Cancer of the Lung
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Large Cell Neuroendocrine Carcinoma of the Lung
Intervention  ICMJE 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.
Study Arms  ICMJE Experimental: Atezolizumab/Platinum/Etoposide
Atezolizumab/Platinum/Etoposide Platinum will be cisplatin or carboplatin at the investigators discretion.
Intervention: Drug: Atezolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 20, 2022)		 67
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 31, 2029
Estimated Primary Completion Date January 31, 2028   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Martin Wermke, MD +49 351 7566 martin.wermke@ukdd.de
Contact: Felix C Saalfeld, MD felix.saalfeld@ukdd.de
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05470595
Other Study ID Numbers  ICMJE TUD-ALPINE-077
2020-002683-31 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Technische Universität Dresden
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Technische Universität Dresden
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Roche Pharma AG
Investigators  ICMJE
Principal Investigator: Martin Wermke, MD Technische Universität Dresden (TUD)
PRS Account Technische Universität Dresden
Verification Date November 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP