Clinical Trials Directory

Trials / Recruiting

RecruitingNCT06137378

European Larynx Organ Preservation Study (ELOS) [MK-3475-C44]

ELOS - Induction Chemotherapy With Docetaxel and Cisplatin Followed by Radiation Compared to Additional PD-1 Inhibition in CPS ≥1 Advanced Laryngeal/Hypopharyngeal Cancer Suitable for Laryngectomy Selected After Early Response Evaluation

Status
Recruiting
Phase
Phase 2
Study type
Interventional
Enrollment
140 (estimated)
Sponsor
University of Leipzig · Academic / Other
Sex
All
Age
18 Years – 70 Years
Healthy volunteers
Not accepted

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.

Conditions

Interventions

TypeNameDescription
BIOLOGICALKEYTRUDA®200 mg KEYTRUDA® i. v. in 3-week cycle (q3w)

Timeline

Start date
2024-04-17
Primary completion
2028-12-01
Completion
2030-12-01
First posted
2023-11-18
Last updated
2024-09-20

Locations

9 sites across 1 country: Germany

Regulatory

Source: ClinicalTrials.gov record NCT06137378. Inclusion in this directory is not an endorsement.