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