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Trial Title: Pemetrexed-free vs. Pemetrexed-based Immunochemotherapy in Metastatic TTF-1 Negative Lung Adenocarcinoma

NCT ID: NCT05689671

Condition: Non-Small Cell Lung Cancer Metastatic

Conditions: Official terms:
Adenocarcinoma
Adenocarcinoma of Lung
Paclitaxel
Carboplatin
Pembrolizumab
Pemetrexed
Atezolizumab

Conditions: Keywords:
NSCLC
checkpoint inhibitors
immunochemotherapy

Study type: Interventional

Study phase: Phase 4

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Atezolizumab
Description: 1200 mg i.v. q3w
Arm group label: Pemetrexed-free Immunochemotherapy (Arm A)

Other name: Tecentriq

Intervention type: Drug
Intervention name: Nab paclitaxel
Description: 100 mg/m² i.v. qw
Arm group label: Pemetrexed-free Immunochemotherapy (Arm A)

Other name: Abraxane

Intervention type: Drug
Intervention name: Carboplatin
Description: AUC 5-6 i.v. q3w
Arm group label: Pemetrexed-free Immunochemotherapy (Arm A)

Intervention type: Drug
Intervention name: Pembrolizumab
Description: 200 mg i.v. q3w
Arm group label: Pemetrexed-based Immunochemotherapy (Arm B)

Other name: Keytruda

Intervention type: Drug
Intervention name: Cisplatin
Description: 75 mg/m² i.v. q3w
Arm group label: Pemetrexed-based Immunochemotherapy (Arm B)

Intervention type: Drug
Intervention name: Carboplatin
Description: AUC 5-6 i.v. q3w
Arm group label: Pemetrexed-based Immunochemotherapy (Arm B)

Intervention type: Drug
Intervention name: Pemetrexed
Description: 500 mg/m² i.v. q3w
Arm group label: Pemetrexed-based Immunochemotherapy (Arm B)

Summary: This is an open-label randomized, controlled, multicenter, phase II trial with two arms. Patients with metastatic TTF-1 negative, treatment-naive lung adenocarcinoma without actionable genomic alterations are randomized in a 1:1 manner to investigate the efficiency of atezolizumab, carboplatin and nab-paclitaxel (Arm A) versus pembrolizumab, cis-/carboplatin and pemetrexed (Arm B) as first-line treatment.

Detailed description: Thyroid transcription factor 1 (TTF-1) is expressed in the majority of lung adenocarcinoma and has a clear prognostic value. Pemetrexed-based immunochemotherapy is a standard of care for advanced lung adenocarcinoma. However, real-world data suggest that TTF-1 negative patients might derive superior outcome using pemetrexed-free regimens. The aim of this study is to compare a pemetrexed-free (Arm A) vs. a pemetrexed-based immunochemotherapy (Arm B) as first-line treatment for metastatic TTF-1 negative lung adenocarcinoma without actionable genomic alterations.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Patient has provided written informed consent 2. Patient* 18 years or older at time of signing the informed consent form 3. Histologically or cytologically confirmed metastatic stage IV non-squamous NSCLC 4. Negative local testing for TTF-1 5. Negative molecular testing for EGFR mutations and ALK rearrangements (tested locally). Exception: In specific individual cases, treatment can be initiated prior to receiving molecular diagnostics after consulting with the sponsor, if the local principal investigator assesses the likelihood of an EGFR mutation or ALK fusion to be negligible. However, this should only be done in exceptional cases if the patient has particularly high demand for treatment. If it is subsequently found that patients are positive for EGFR mutations and/or ALK rearrangements, they must be withdrawn from the study immediately and must not receive any further study medication. Instead, patients should receive adequate SOC therapy outside the study. Awaiting results for molecular testing remains standard procedure for patient inclusion. 6. PD-L1 tumor proportion score (TPS) < 50%, tested locally by QUiP®-certified immunohistochemistry 7. ECOG performance status ≤ 1 8. Measurable lesions according to RECIST v1.1 9. Life expectancy ≥ 12 weeks 10. Adequate hepatic, renal and bone marrow function 1. Hemoglobin ≥ 8.0 g/dL 2. Absolute neutrophil count ≥ 1.5 x 109/L 3. Platelets ≥ 100 x 109/L 4. Calculated creatine clearance ≥ 50 mL/min as determined by the Cockcroft-Gault equation and/or creatinin ≤ 1,5x upper limit of normal (ULN) 5. Serum bilirubin ≤ 1.5 x institutional ULN 6. AST/ ALT and alkaline phosphatase ≤ 2.5 x ULN 7. International normalized ratio (INR)/ Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PTT is within therapeutic range of intended use of anticoagulants 11. The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations. 12. Female patients who are considered as woman of childbearing potential (WOCBP) must use any contraceptive method with a failure rate of less than 1% per year during the treatment as well as up to 6 months after the last dose of study treatment. Male patients who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year during the treatment as well as at least 6 months after the last dose of IMP. Female patients who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) as well as azoospermic male patients do not require contraception Exclusion Criteria: 1. Mixed histologies (small-cell and non-small cell or non-squamous and squamous; patients exhibiting the latter expression pattern may be eligible if the non-squamous part predominates) 2. Patients having received: 1. Systemic treatment for metastatic or locally advanced disease 2. prior PD-1/PD-L1 immunotherapies (prior treatment with CD137 agonists or immune checkpoint blockade therapies, including, but not limited to, anti-cytotoxic T lymphocyte associated protein 4 [anti-CTLA-4], anti T cell immunoreceptor with Ig and tyrosine-based inhibition motif domains [anti-TIGIT], anti-PD-1 and anti-PD-L1 therapeutic antibodies) 3. Symptomatic, neurologically unstable CNS metastases or requiring increasing doses of steroids to manage CNS symptoms within 2 weeks prior to study entry (maximal acceptable dose must be ≤ 10 mg of prednisolone). Patients with asymptomatic, incidentally detected CNS metastases may be enrolled. Palliative radiotherapy for asymptomatic brain metastases (and any other, non-brain metastases, e.g. bone metastases) may be conducted after study entry. 4. Leptomeningeal disease 5. History of interstitial lung disease 6. Severe infection within 2 weeks prior to study entry. Clinical signs must have been resolved to CTCAE grade ≤ 1 7. Active infection with hepatitis B or C virus (HBV, HCV), human immunodeficiency virus (HIV) or Mycobacterium tuberculosis 8. Known additional malignancies other than NSCLC, either untreated or having required active treatment within the past 3 years 9. Significant cardiovascular disease (≥ NYHA 3) 10. Active or prior documented autoimmune or inflammatory disorders (including but not limited to diverticulitis [with the exception of diverticulosis], celiac disease, systemic lupus erythematosus, Sarcoidosis, or Wegener's syndrome [granulomatosis with polyangiitis], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis). The following are exceptions to this criterion: 1. Patients with vitiligo or alopecia 2. Patients with hypothyroidism (e.g., following Hashimoto's disease) stable on hormone replacement 3. Patients with controlled Type I diabetes mellitus on an insulin regimen 4. Any chronic skin condition that does not require systemic therapy 5. Patients without active disease in the last 5 years may be included but only after consultation with the study physician 11. Current or prior use of immunosuppressive medication within 14 days before the first dose of atezolizumab/pembrolizumab. The following are exceptions to this criterion: 1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra articular injection) 2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent 3. Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication) 12. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment 13. Live vaccine within 30 days prior to first dose of trial treatment 14. Known allergy or hypersensitivity to any component of the chemotherapy regimen or to atezolizumab or pembrolizumab or any constituents of the products 15. Any co-existing medical condition that in the investigator's judgement will substantially increase the risk associated with the patient's participation in the study. 16. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Klinikum St. Marien

Address:
City: Amberg
Zip: 92224
Country: Germany

Status: Recruiting

Contact:
Last name: Ludwig Fischer von Weikersthal, Dr. med.

Facility:
Name: MVZ Taunus GmbH

Address:
City: Bad Homburg
Zip: 61352
Country: Germany

Status: Recruiting

Contact:
Last name: Migle Link, Dr. med.

Facility:
Name: Evangelische Lungenklinik Krankenhausbetriebs gGmbH

Address:
City: Berlin
Zip: 13125
Country: Germany

Status: Recruiting

Contact:
Last name: Christian Grohé, Prof. Dr.

Facility:
Name: Evangelische Lungenklinik

Address:
City: Berlin
Zip: 13125
Country: Germany

Status: Recruiting

Contact:
Last name: Christian Grohé, Prof. Dr.

Facility:
Name: Charité Universitätsmedizin

Address:
City: Berlin
Zip: 13353
Country: Germany

Status: Recruiting

Contact:
Last name: Nikolaj Frost, Dr.

Facility:
Name: Helios Klinikum Emil von Behring

Address:
City: Berlin
Zip: 14165
Country: Germany

Status: Recruiting

Contact:
Last name: Jens Kollmeier, Dr.

Facility:
Name: Klinikum Bielefeld

Address:
City: Bielefeld
Zip: 33604
Country: Germany

Status: Recruiting

Contact:
Last name: Martin Görner, Dr.

Facility:
Name: Technische Universität Dresden Medizinische Fakultät Carl Gustav Carus

Address:
City: Dresden
Zip: 01307
Country: Germany

Status: Recruiting

Contact:
Last name: Felix Saalfeld, Dr.

Facility:
Name: KEM Evang. Kliniken Essen-Mitte

Address:
City: Essen
Zip: 45136
Country: Germany

Status: Recruiting

Contact:
Last name: Sebastian Ertl, Dr.

Facility:
Name: Klinikum Esslingen GmbH

Address:
City: Esslingen
Zip: 73730
Country: Germany

Status: Recruiting

Contact:
Last name: Martin Faehling, PD Dr.

Facility:
Name: Universitätsklinikum Frankfurt am Main

Address:
City: Frankfurt am Main
Zip: 60590
Country: Germany

Status: Recruiting

Contact:
Last name: Martin Sebastian, Dr. med.

Facility:
Name: Krankenhaus Nordwest

Address:
City: Frankfurt
Zip: 60488
Country: Germany

Status: Recruiting

Contact:
Last name: Akin Atmaca, PD DR.

Facility:
Name: Asklepios Klinik Gauting GmbH

Address:
City: Gauting
Zip: 82131
Country: Germany

Status: Recruiting

Contact:
Last name: Niels Reinmuth, Prof. Dr.

Facility:
Name: LungenClinic Großhansdorf GmbH

Address:
City: Großhansdorf
Zip: 22927
Country: Germany

Status: Recruiting

Contact:
Last name: Martin Reck, Prof. Dr.

Facility:
Name: Universitätsmedizin Göttingen

Address:
City: Göttingen
Zip: 37075
Country: Germany

Status: Recruiting

Contact:
Last name: Tobias Overbeck, Dr.

Facility:
Name: Asklepios Klinkum Hamburg

Address:
City: Hamburg
Zip: 21075
Country: Germany

Status: Recruiting

Contact:
Last name: Claas Wesseler, Dr.

Facility:
Name: Thoraxklinik Heidelberg gGmbH

Address:
City: Heidelberg
Zip: 69126
Country: Germany

Status: Recruiting

Contact:
Last name: Farastuk Bozorgmehr, Dr.

Facility:
Name: Lungenklinik Hemer

Address:
City: Hemer
Zip: 58675
Country: Germany

Status: Recruiting

Contact:
Last name: Karsten Schulmann, PD Dr. med.

Facility:
Name: Helios Klinikum Krefeld

Address:
City: Krefeld
Zip: 47805
Country: Germany

Status: Recruiting

Contact:
Last name: Benoit Krämer

Facility:
Name: Kliniken der Stadt Köln GmbH

Address:
City: Köln
Zip: 51109
Country: Germany

Status: Recruiting

Contact:
Last name: Carolin Groß-Ophoff-Müller, Dr. med.

Facility:
Name: ÜBAG- Medizinisches Versorgungszentrum Dr. Vehling-Kaiser GmbH

Address:
City: Landshut
Zip: 84036
Country: Germany

Status: Recruiting

Contact:
Last name: Florian Kaiser, Dr.

Facility:
Name: Klinikum Lippe GmbH

Address:
City: Lemgo
Zip: 32657
Country: Germany

Status: Recruiting

Contact:
Last name: Christian Constantin, Dr.

Facility:
Name: Klinikum Ludwigsburg

Address:
City: Ludwigsburg
Zip: 71640
Country: Germany

Status: Recruiting

Contact:
Last name: Matthias Ulmer, Dr.

Facility:
Name: UKSH, Campus Lübeck

Address:
City: Lübeck
Zip: 23538
Country: Germany

Status: Recruiting

Contact:
Last name: Sabine Bohnert, Dr.

Facility:
Name: Medizinische Fakultät Mannheim der Universität Heidelberg

Address:
City: Mannheim
Zip: 68167
Country: Germany

Status: Recruiting

Contact:
Last name: Melanie Janning, Dr.

Facility:
Name: LMU Klinikum

Address:
City: München
Zip: 80336
Country: Germany

Status: Recruiting

Contact:
Last name: Amanda Tufman, Prof. Dr.

Facility:
Name: Unversitätsklinikum Münster

Address:
City: Münster
Zip: 48149
Country: Germany

Status: Recruiting

Contact:
Last name: Annalen Bleckmann, Prof. Dr.

Facility:
Name: Überörtliche Gemeinschaftspraxis für Hämatologie und Onkologie

Address:
City: Münster
Zip: 48153
Country: Germany

Status: Recruiting

Contact:
Last name: Rüdiger Liersch, PD Dr.

Facility:
Name: Pius Hospital

Address:
City: Oldenburg
Zip: 26121
Country: Germany

Status: Recruiting

Contact:
Last name: Frank Griesinger, Prof. Dr.

Facility:
Name: Barmherzige Brüder Krankenhaus Regensburg

Address:
City: Regensburg
Zip: 93049
Country: Germany

Status: Recruiting

Contact:
Last name: Veronika Berberich, Dr.

Facility:
Name: Elblandkliniken Stiftung & Co. KG Elblandklinikum Riesa

Address:
City: Riesa
Zip: 01589
Country: Germany

Status: Recruiting

Contact:
Last name: Jörg Schubert, Prof. Dr.

Start date: December 6, 2023

Completion date: October 2026

Lead sponsor:
Agency: Nikolaj Frost MD
Agency class: Other

Collaborator:
Agency: Roche Pharma AG
Agency class: Industry

Collaborator:
Agency: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Agency class: Other

Source: Charite University, Berlin, Germany

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05689671
https://www.aio-portal.de/studie/176--antelope.html

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