Trial Title:
European Larynx Organ Preservation Study (ELOS) [MK-3475-C44]
NCT ID:
NCT06137378
Condition:
Squamous Cell Carcinoma of Head and Neck
Hypopharyngeal Squamous Cell Carcinoma
Laryngeal Squamous Cell Carcinoma Stage III
Laryngeal Squamous Cell Carcinoma Stage IV
Squamous Cell Carcinoma of Larynx
Squamous Cell Carcinoma of the Larynx
Squamous Cell Carcinoma of the Larynx Stage III
Squamous Cell Carcinoma of the Larynx Stage IV
Laryngeal Squamous Cell Carcinoma
Laryngectomy; Status
Laryngeal Cancer
Laryngeal Neoplasms
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Laryngeal Neoplasms
Squamous Cell Carcinoma of Head and Neck
Laryngeal Diseases
Pembrolizumab
Conditions: Keywords:
induction chemotherapy
neoadjuvant treatment
immune checkpoint inhibitor
pembrolizumab
KEYNOTE
larynx organ preservation
laryngectomy-free survival
overall survival
event-free survival
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Prospective, randomized, open-label, controlled, two-armed parallel group, phase II
multicenter larynx organ-preservation trial with randomization in a 1:1 ratio into
standard arm vs. investigational arm with a flexible follow-up of 24-48 months
Primary purpose:
Treatment
Masking:
None (Open Label)
Masking description:
There will be no masking
Intervention:
Intervention type:
Biological
Intervention name:
KEYTRUDA®
Description:
200 mg KEYTRUDA® i. v. in 3-week cycle (q3w)
Arm group label:
B - KEYTRUDA®
Other name:
Pembrolizumab
Other name:
MK-3475
Summary:
ELOS is a prospective, randomized, open-label, controlled, two-armed parallel group,
phase II multicentre trial in local advanced stage III, IVA/B head and neck squamous cell
carcinoma of the larynx or hypopharynx (LHNSCC) with PD-L1-expression within tumor tissue
biopsy, calculated as CPS ≥ 1 curable by total laryngectomy. Induction chemotherapy (IC)
with Docetaxel and Cisplatin (TP) followed by radiation will be compared to additional
PD-1 inhibition. Patients will be selected after short induction early response
evaluation after the first cycle IC (IC-1) aiming on larynx organ-preservation by
additional 2 cycles IC followed by radiotherapy (69.6 Gy) for responders achieving
endoscopic estimated tumor surface shrinkage (ETSS) ≥ 30%. Nonresponders (ETSS < 30% or
progressing disease) will receive total laryngectomy and selective neck dissection
followed by postoperative radiation or chemoradiation according to the recommendation of
the clinics multidisciplinary tumor board. However, Patients randomized into the
intervention arm starting day 1 will receive 200 mg Pembrolizumab (MK-3475) i.v. in
3-week cycle (q3w) 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.
Detailed description:
ELOS is a prospective, randomized, open-label, controlled, two-armed parallel group,
phase II multicentre trial in local advanced stage III, IVA/B head and neck squamous cell
carcinoma of the larynx or hypopharynx (LHNSCC) with PD-L1-expression within tumor tissue
biopsy, calculated as CPS ≥ 1 curable by total laryngectomy. Induction chemotherapy (IC)
with Docetaxel and Cisplatin (TP) followed by radiation will be compared to additional
PD-1 inhibition. Patients will be selected after short induction early response
evaluation after the first cycle IC (IC-1) aiming on larynx organ-preservation by
additional 2 cycles IC followed by radiotherapy (69.6 Gy) for responders achieving
endoscopic estimated tumor surface shrinkage (ETSS) ≥ 30%. Nonresponders (ETSS < 30% or
progressing disease) will receive total laryngectomy and selective neck dissection
followed by postoperative radiation or chemoradiation according to the recommendation of
the clinics multidisciplinary tumor board. However, Patients randomized into the
intervention arm starting day 1 will receive 200 mg Pembrolizumab (MK-3475) i.v. in
3-week cycle (q3w) 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.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Participants are eligible to be included in the study only if all of the following
criteria apply:
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:
Participants are excluded from the study if any of the following criteria apply:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Universitätsklinikum Mannheim, Klinik für Hals-Nasen-Ohrenheilkunde Theodor-Kutzer-Ufer 1-3
Address:
City:
Mannheim
Zip:
68167
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Annette Affolter, PD Dr.
Phone:
+49 621 383 3965
Email:
Annette.Affolter@umm.de
Contact backup:
Last name:
Nicole Rotter, Prof. Dr.
Phone:
+49 621 383 3965
Email:
nicole.rotter@umm.de
Investigator:
Last name:
Annette Affolter, PD Dr.
Email:
Principal Investigator
Investigator:
Last name:
Nicole Rotter, Prof. Dr.
Email:
Sub-Investigator
Facility:
Name:
Universitätsklinikum Ulm / Ulm University Medical Center, Klinik für Hals- Nasen-Ohrenheilkunde und Kopf-Halschirurgie, Frauensteige 12
Address:
City:
Ulm
Zip:
89075
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Simon Laban, Prof. Dr.
Phone:
+49 731 50059500
Email:
Simon.Laban@uniklinik-ulm.de
Contact backup:
Last name:
Thomas Hoffmann, Prof. Dr.
Phone:
+49 731 50059500
Email:
t.hoffmann@uniklinik-ulm.de
Investigator:
Last name:
Simon Laban, Prof. Dr.
Email:
Principal Investigator
Investigator:
Last name:
Thomas Hoffmann, Prof.Dr.
Email:
Sub-Investigator
Facility:
Name:
Klinikum rechts der Isar der TU München, Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde, Ismaninger Straße 22
Address:
City:
München
Zip:
81675
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Barbara Wollenberg, Prof. Dr.
Phone:
004989-4140 2370
Email:
barbara.wollenberg@tum.de
Contact backup:
Last name:
Markus Wirth, PD Dr.
Phone:
004989-4140 2370
Email:
Markus.Wirth@tum.de
Investigator:
Last name:
Barbara Wollenberg, Prof. Dr.
Email:
Principal Investigator
Investigator:
Last name:
Markus Wirth, PD Dr.
Email:
Sub-Investigator
Facility:
Name:
Universität Regensburg, Klinik und Poliklinik für Strahlentherapie Franz-Josef-Strauss-Allee 11
Address:
City:
Regensburg
Zip:
93053
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Christoph Süß, Dr. med.
Phone:
+49 941 944-9400
Email:
Christoph.Suess@ukr.de
Contact backup:
Last name:
Felix Kajetan Steger, Dr. med.
Phone:
+49 941 944-9400
Email:
Felix.Steger@ukr.de
Investigator:
Last name:
Christoph Süß, Dr. med.
Email:
Principal Investigator
Investigator:
Last name:
Felix Kajetan Steger, Dr. med.
Email:
Sub-Investigator
Facility:
Name:
Universitätsklinikum Würzburg, Klinik für Hals-, Nasen-, Ohrenheilkunde, Josef-Schneider-Straße 8
Address:
City:
Würzburg
Zip:
97080
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Thomas Gehrke, PD Dr.
Phone:
0049931-201 21757
Email:
Gehrke_T@ukw.de
Contact backup:
Last name:
Matthias Scheich, PD Dr.
Phone:
0049931-201 21707
Email:
Scheich_M@ukw.de
Investigator:
Last name:
Thomas Gehrke, PD Dr.
Email:
Principal Investigator
Investigator:
Last name:
Matthias Scheich, PD Dr.
Email:
Sub-Investigator
Facility:
Name:
Klinikum Ernst von Bergmann, Klinik für Hämatologie, Onkologie und Palliativmedizin, Charlottenstr. 72
Address:
City:
Potsdam
Zip:
14467
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Grzegorz Kofla, Dr. med.
Phone:
0049331-241 35702
Email:
Grzegorz.Kofla@klinikumevb.de
Contact backup:
Last name:
Karin Jordan, Prof. Dr.
Phone:
0049331-241 35700
Email:
Karin.Jordan@klinikumevb.de
Investigator:
Last name:
Grzegorz Kofla, Dr. med.
Email:
Principal Investigator
Investigator:
Last name:
Karin Jordan, Prof. Dr.
Email:
Sub-Investigator
Facility:
Name:
Universitätsklinikum Köln, Klinik für Hals-, Nasen-, Ohrenheilkunde, Kerpener Str. 62
Address:
City:
Köln
Zip:
50937
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Shachi Sharma, Dr. med.
Phone:
0049221-478 4750
Email:
shachi.sharma@uk-koeln.de
Contact backup:
Last name:
Jens Peter Klußmann, Prof. Dr.
Phone:
0221-478 51660
Email:
jens.klussmann@uk-koeln.de
Investigator:
Last name:
Shachi Sharma, Dr. med.
Email:
Principal Investigator
Investigator:
Last name:
Jens Peter Klußmann, Prof. Dr.
Email:
Sub-Investigator
Facility:
Name:
University of Leipzig, Department für Kopf- und Zahnmedizin, Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde, Liebigstrasse 12
Address:
City:
Leipzig
Zip:
04103
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Andreas Dietz, Prof. Dr.
Phone:
+493419721700
Email:
andreas.dietz@medizin.uni-leipzig.de
Contact backup:
Last name:
Markus Pirlich, PD Dr.
Phone:
03419721700
Email:
markus.pirlich@medizin.uni-leipzig.de
Investigator:
Last name:
Andreas Dietz, Prof. Dr.
Email:
Principal Investigator
Investigator:
Last name:
Markus Pirlich, PD Dr.
Email:
Sub-Investigator
Investigator:
Last name:
Theresa Wald, Dr.
Email:
Sub-Investigator
Facility:
Name:
Universitätsklinikum Jena Klinik für Hals-, Nasen- und Ohrenheilkunde, Am Klinikum 1
Address:
City:
Jena
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Orlando Guntinas-Lichius, Prof. Dr.
Phone:
00493641-9329301
Email:
orlando.guntinas@med.uni-jena.de
Contact backup:
Last name:
Thomas Bitter, PD Dr.
Phone:
00493641-9329300
Email:
thomas.bitter@med.uni-jena.de
Investigator:
Last name:
Orlando Guntinas-Lichius, Prof. Dr.
Email:
Principal Investigator
Investigator:
Last name:
Thomas Bitter, PD Dr.
Email:
Sub-Investigator
Start date:
April 17, 2024
Completion date:
December 2030
Lead sponsor:
Agency:
University of Leipzig
Agency class:
Other
Collaborator:
Agency:
University of Göttingen
Agency class:
Other
Collaborator:
Agency:
University of Jena
Agency class:
Other
Collaborator:
Agency:
University of Cologne
Agency class:
Other
Collaborator:
Agency:
University of Ulm
Agency class:
Other
Collaborator:
Agency:
University of Regensburg
Agency class:
Other
Collaborator:
Agency:
Wuerzburg University Hospital
Agency class:
Other
Collaborator:
Agency:
Technical University of Munich
Agency class:
Other
Collaborator:
Agency:
Ernst von Bergmann Hospital
Agency class:
Other
Collaborator:
Agency:
Universitätsmedizin Mannheim
Agency class:
Other
Collaborator:
Agency:
University of Kiel
Agency class:
Other
Source:
University of Leipzig
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06137378
