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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05689671
Other study ID # SAP131705
Secondary ID 2022-002990-27AI
Status Recruiting
Phase Phase 4
First received
Last updated
Start date December 6, 2023
Est. completion date October 2026

Study information

Verified date April 2024
Source Charite University, Berlin, Germany
Contact Nikolaj Frost, PD Dr.
Phone +49 30 450 565 005
Email nikolaj.frost@charite.de
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 136
Est. completion date October 2026
Est. primary completion date October 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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) 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 central nervous system (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) 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Atezolizumab
1200 mg i.v. q3w
Nab paclitaxel
100 mg/m² i.v. qw
Carboplatin
AUC 5-6 i.v. q3w
Pembrolizumab
200 mg i.v. q3w
Cisplatin
75 mg/m² i.v. q3w
Carboplatin
AUC 5-6 i.v. q3w
Pemetrexed
500 mg/m² i.v. q3w

Locations

Country Name City State
Germany Klinikum St. Marien Amberg
Germany MVZ Taunus GmbH Bad Homburg
Germany Charité Universitätsmedizin Berlin
Germany Evangelische Lungenklinik Berlin
Germany Evangelische Lungenklinik Krankenhausbetriebs gGmbH Berlin
Germany Helios Klinikum Emil von Behring Berlin
Germany Klinikum Bielefeld Bielefeld
Germany Technische Universität Dresden Medizinische Fakultät Carl Gustav Carus Dresden
Germany KEM Evang. Kliniken Essen-Mitte Essen
Germany Klinikum Esslingen GmbH Esslingen
Germany Krankenhaus Nordwest Frankfurt
Germany Universitätsklinikum Frankfurt am Main Frankfurt am Main
Germany Asklepios Klinik Gauting GmbH Gauting
Germany Universitätsmedizin Göttingen Göttingen
Germany LungenClinic Großhansdorf GmbH Großhansdorf
Germany Asklepios Klinkum Hamburg Hamburg
Germany Thoraxklinik Heidelberg gGmbH Heidelberg
Germany Lungenklinik Hemer Hemer
Germany Kliniken der Stadt Köln GmbH Köln
Germany Helios Klinikum Krefeld Krefeld
Germany ÜBAG- Medizinisches Versorgungszentrum Dr. Vehling-Kaiser GmbH Landshut
Germany Klinikum Lippe GmbH Lemgo
Germany UKSH, Campus Lübeck Lübeck
Germany Klinikum Ludwigsburg Ludwigsburg
Germany Medizinische Fakultät Mannheim der Universität Heidelberg Mannheim
Germany LMU Klinikum München
Germany Überörtliche Gemeinschaftspraxis für Hämatologie und Onkologie Münster
Germany Unversitätsklinikum Münster Münster
Germany Pius Hospital Oldenburg
Germany Barmherzige Brüder Krankenhaus Regensburg Regensburg
Germany Elblandkliniken Stiftung & Co. KG Elblandklinikum Riesa Riesa

Sponsors (3)

Lead Sponsor Collaborator
Nikolaj Frost MD Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest, Roche Pharma AG

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Frost N, Zhamurashvili T, von Laffert M, Klauschen F, Ruwwe-Glosenkamp C, Raspe M, Brunn M, Ochsenreither S, Temmesfeld-Wollbruck B, Suttorp N, Grohe C, Witzenrath M. Pemetrexed-Based Chemotherapy Is Inferior to Pemetrexed-Free Regimens in Thyroid Transcription Factor 1 (TTF-1)-Negative, EGFR/ALK-Negative Lung Adenocarcinoma: A Propensity Score Matched Pairs Analysis. Clin Lung Cancer. 2020 Nov;21(6):e607-e621. doi: 10.1016/j.cllc.2020.05.014. Epub 2020 May 22. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Overall Survival (OS) time from randomization to the date of death due to any case 30 months
Secondary Objectice Response Rate (ORR) proportion of subjects with best response of complete or partial response (CR & PR) according to RECIST v1.1 30 months
Secondary Progression-Free Survival (PFS) time from randomization until progression defined by RECIST v1.1 or death due to any cause 30 months
Secondary One-Year Overall Survival Rate percentage of patients alive at 12 months after randomization 30 months
Secondary Time to Next Treatment or Death (TNTD) time from initial study randomization to the start of next subsequent treatment or death, whichever occurs first 30 months
Secondary Progression-Free Survival 2 (PFS2) time from initial study randomization to second disease progression or death from any cause to assess efficacy post-trial-treatment anti-cancer therapy 30 months
Secondary Health-related quality of life 1 (HRQoL) assessed with the QoL questionnaire QLQ-C30 on general health conditions in lung cancer patients using numeric scales ranging from 1-4. Lower numbers indicate no, higher numbers high agreement. Assessed after randomization at cycle 1 day 1, after completion of cycle 4 (each cycle is 21 days) of the chemoimmunotherapy and at progressive disease (if occurring within the maximum time frame of 30 months)
Secondary Health-related quality of life 2 (HRQoL) assessed with the lung cancer symptom-specific QoL questionnaire QLQ-LC13 using numeric scales ranging from 1-4. Lower numbers indicate no, higher numbers high agreement. Assessed after randomization at cycle 1 day 1, after completion of cycle 4 (each cycle is 21 days) of the chemoimmunotherapy and at progressive disease (if occurring within the maximum time frame of 30 months)
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