European Larynx Organ Preservation Study (ELOS) [MK-3475-C44]
NCT ID: NCT06137378
Last Updated: 2024-09-20
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
140 participants
INTERVENTIONAL
2024-04-17
2030-12-31
Brief Summary
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Detailed Description
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The primary objective of ELOS is to compare laryngectomy-free survival (LFS) achieved by adding KEYTRUDA® (pembrolizumab) to standard treatment and LFS after standard treatment according to the DeLOS-II protocol in advanced LHNSCC curable by laryngectomy.
Hypothesis: Adding PD-1 inhibition by pembrolizumab to organ-preservation chemoradiation treatment improves laryngectomy-free survival (LFS) compared to standard treatment according to the DeLOS-II protocol.
The secondary objectives are to compare Quality of Swallowing (QoS) assessed by FEES, event free survival (EFS) and overall survival (OS) achieved by adding KEYTRUDA® (pembrolizumab) to standard treatment and QoS, EFS and OS after standard treatment according to the DeLOS-II protocol in advanced LHNSCC. In general, the main interest in trials focusing on improving quality and degree of larynx organ preservation is late functional (in particular "swallowing") outcome. Current instruments assessing hrQoL are less meaningful than direct objective assessment of swallowing utilizing physical examination like FEES. FEES is a well approved and reliable method and allows clear scoring of quality of swallowing for instance by applying the Rosenbek Scale. Therefore, the investigators decided to avoid any questionnaires for this assessment including those approved for use in head and neck cancer, as they fail to specifically address the main study outcome, functional larynx organ preservation.
Hypothesis: Adding PD-1 inhibition by KEYTRUDA® (pembrolizumab) to organ-preservation chemoradiation treatment improves QoS, EFS and OS compared to standard treatment according to the DeLOS-II protocol. EFS events are defined as any event either in interfering with proper larynx organ function (independent of the cause, tumor- or treatment related), relapse (local, loco-regional, or distant), or death.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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A - Control
Standard-Arm:
Short Induction (IC-1):
T = Docetaxel 75 mg/m\^2 i.v. day 1 P = Cisplatin 75 mg/m\^2 i.v. day 1 Response evaluation will be performed in week 4 after IC-1 by endoscopic estimation of tumor-surface shrinkage (ETSS) to select nonresponders for early total laryngectomy (TL). Responders receive further 2 cycles TP followed by radiotherapy (RT) starting week 11.
ETSS \< 30% (Nonresponder):
\- TL + adjuvant RT or chemo-radiotherapy (CRT) according the decision of the tumor board
ETSS \>=30% (Responder):
2 further TP cycles (IC-2 in week 5-7 and IC-3 in week 8-10; same doses as IC-1) Radiotherapy (RT) is accelerated IMRT with concomitant boost with total dose of 69.6 Gy applied over 5.5 weeks to all tumor localizations; clinically non-affected neck levels receive 51.6 Gy.
\* protocol is according exactly to the DeLOS-II protocol arm A in Dietz et al. Ann Oncol. 2018 Oct 1;29(10):2105-2114
No interventions assigned to this group
B - KEYTRUDA®
Intervention arm aka Experimental-Arm:
Treatment same as for patients randomized into the standard arm A + application of KEYTRUDA® (pembrolizumab), i.v., in 3-week cycle (q3w) 200 mg, starting day 1; for 17 cycles (12 months). Treatment with pembrolizumab will continue in the experimental arm regardless of ETSS status after IC-1 in both responders and laryngectomized nonresponders, independent from subsequent decision on adjuvant therapy after TL.
KEYTRUDA®
200 mg KEYTRUDA® i. v. in 3-week cycle (q3w)
Interventions
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KEYTRUDA®
200 mg KEYTRUDA® i. v. in 3-week cycle (q3w)
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
1. Male and female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of squamous cell carcinoma (SCC) of the larynx or hypopharynx according to the decision of the multidisciplinary tumor board suitable for total laryngectomy can be enrolled in this study.
2. Stage III, IVA or IVB, whenever clear resection margins R0 \>5 mm can be achieved and no radiologic signs of extranodal extension of neck nodes are present.
3. Have provided newly obtained excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
4. PD-L1-expression\* within the tumor biopsy, CPS ≥1
5. Male participants:
A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
6. Female participants:
A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) OR
2. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation/randomization.
8. Have adequate organ function as defined in the (Table 4) of the protocol. Specimens must be collected within 10 days prior to the start of study treatment.
Exclusion Criteria
1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to receiving the first dose of study medication (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory receptor on T or NK cells (e.g., CTLA-4, OX 40, CD137).
3. Has received prior systemic anti-cancer therapy including investigational agents.
4. Has received prior radiotherapy.
5. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
6. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
8. Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
9. Has known distant metastases including active CNS metastases and/or carcinomatous meningitis.
10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
11. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
12. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
13. Has an active infection requiring systemic therapy.
14. Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority.
15. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
16. Has a known history of active TB (Bacillus Tuberculosis).
17. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
18. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
19. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
20. Has had an allogenic tissue/solid organ transplant.
21. Has a known intolerance to one of the substances administered during treatment including e.g. antibiotics, antiemetics, etc. or any other component of concurrent auxiliary medication.
18 Years
70 Years
ALL
No
Sponsors
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University of Göttingen
OTHER
University of Jena
OTHER
University of Cologne
OTHER
University of Ulm
OTHER
University of Regensburg
OTHER
Wuerzburg University Hospital
OTHER
Technical University of Munich
OTHER
Ernst von Bergmann Hospital
OTHER
Universitätsmedizin Mannheim
OTHER
University of Kiel
OTHER
University of Leipzig
OTHER
Responsible Party
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Andreas Dietz
Univ.-Prof. Dr. med. Andreas Dietz, Chairman, Clinic of Otolaryngology, Head and Neck Surgery & Dept. Head Medicine and Oral Health
Locations
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Universitätsklinikum Mannheim, Klinik für Hals-Nasen-Ohrenheilkunde Theodor-Kutzer-Ufer 1-3
Mannheim, Baden-Würtemberg, Germany
Universitätsklinikum Ulm / Ulm University Medical Center, Klinik für Hals- Nasen-Ohrenheilkunde und Kopf-Halschirurgie, Frauensteige 12
Ulm, Baden-Würtemberg, Germany
Klinikum rechts der Isar der TU München, Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde, Ismaninger Straße 22
München, Bavaria, Germany
Universität Regensburg, Klinik und Poliklinik für Strahlentherapie Franz-Josef-Strauss-Allee 11
Regensburg, Bavaria, Germany
Universitätsklinikum Würzburg, Klinik für Hals-, Nasen-, Ohrenheilkunde, Josef-Schneider-Straße 8
Würzburg, Bavaria, Germany
Klinikum Ernst von Bergmann, Klinik für Hämatologie, Onkologie und Palliativmedizin, Charlottenstr. 72
Potsdam, Brandenburg, Germany
Universitätsklinikum Köln, Klinik für Hals-, Nasen-, Ohrenheilkunde, Kerpener Str. 62
Cologne, North Rhine-Westphalia, Germany
University of Leipzig, Department für Kopf- und Zahnmedizin, Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde, Liebigstrasse 12
Leipzig, Saxon, Germany
Universitätsklinikum Jena Klinik für Hals-, Nasen- und Ohrenheilkunde, Am Klinikum 1
Jena, Thuringia, Germany
Countries
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Central Contacts
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Facility Contacts
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References
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Dietz A, Wichmann G, Kuhnt T, Pfreundner L, Hagen R, Scheich M, Kolbl O, Hautmann MG, Strutz J, Schreiber F, Bockmuhl U, Schilling V, Feyer P, de Wit M, Maschmeyer G, Jungehulsing M, Schroeder U, Wollenberg B, Sittel C, Munter M, Lenarz T, Klussmann JP, Guntinas-Lichius O, Rudack C, Eich HT, Foerg T, Preyer S, Westhofen M, Welkoborsky HJ, Esser D, Thurnher D, Remmert S, Sudhoff H, Gorner M, Bunzel J, Budach V, Held S, Knodler M, Lordick F, Wiegand S, Vogel K, Boehm A, Flentje M, Keilholz U. Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II. Ann Oncol. 2018 Oct 1;29(10):2105-2114. doi: 10.1093/annonc/mdy332.
Bindewald J, Herrmann E, Dietz A, Wulke C, Meister E, Wollbruck D, Singer S. [Quality of life and voice intelligibility in laryngeal cancer patients--relevance of the "satisfaction paradox"]. Laryngorhinootologie. 2007 Jun;86(6):426-30. doi: 10.1055/s-2007-966167. German.
Rosenbek JC, Robbins JA, Roecker EB, Coyle JL, Wood JL. A penetration-aspiration scale. Dysphagia. 1996 Spring;11(2):93-8. doi: 10.1007/BF00417897.
Wichmann G, Wald T, Pirlich M, Napp J, Munter I, Asendorf T, Tostmann R, Vogt J, Vogel K, Meuret S, Stoehr M, Zebralla V, Nicolay NH, Kuhnt T, Hambsch P, Guntinas-Lichius O, Klussmann JP, Wiegand S, Dietz A. The European Larynx Organ Preservation Study [MK-3475-C44]. Front Oncol. 2024 Aug 22;14:1433238. doi: 10.3389/fonc.2024.1433238. eCollection 2024.
Other Identifiers
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2022-502751-61-00
Identifier Type: OTHER
Identifier Source: secondary_id
P_00432
Identifier Type: OTHER
Identifier Source: secondary_id
2022-502751-61-00
Identifier Type: -
Identifier Source: org_study_id
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