NCT05930938

Study Comparing RT With Cetuximab + Xevinapant to RT With Cetuximab-placebo in Patients With Head and Neck Cancer

A Double-blind, Randomized, Phase III Study of Radiotherapy Combined With cetuXimab + Xevinapant Compared to Radiotherapy Combined With Cetuximab (Standard of Care) + Placebo in Patients With LA SCCHN, Unfit for High-dose Cisplatin

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: Groupe Oncologie Radiotherapie Tete et Cou · Academic / Other
• Sex: All
• Age: 18 Years – 79 Years
• Healthy volunteers: Not accepted

Summary

Xevinapant is an antagonist of inhibitor of apoptosis proteins (IAPs) that has been shown both chemo-, radiosensitizing, and immunomodulatory activities in nonclinical in vitro and in vivo squamous cell carcinoma of the head and neck (SCCHN) models. In previously untreated patients with non-resected locally advanced SCCHN, the addition of xevinapant recently showed a significant improvement of progression-free survival (PFS), overall survival (OS) and loco-regional control at 3 years after completing treatment. Thus, the purpose of this Phase III study is to demonstrate the superior efficacy to the xevinapant when it is administered in combination with radiotherapy (RT)+cetuximab compared to radiotherapy+cetuximab (SoC) + placebo in previously untreated participants with LA-SCCHN, ineligible for high-dose cisplatin defined as ≥ 200 mg/m² (projective total cumulative dose) throughout the course of the radiotherapy.

Detailed description

CT-RT and especially cisplatin-RT is a well-established and the most commonly used SoC for patients with LA SCCHN15. However, a large proportion of patients with LA SCCHN are not suitable for high dose platin based CT-RT for several reasons (age, medical/general conditions and or comorbidities…). Based on recent GORTEC study, the proportion of patients unfit for receiving high-dose of cisplatin was 43% among 707 patients randomized19. In the corresponding cohort of the REACH study, the characteristics of the population (same population to be included in the XXL study) were fragile patients, unfit for high-dose cisplatin, with heavy alcohol and tobacco consumption, numerous comorbidities and a median age 67 years. In this population, there was a trend in the triplet combination of cetuximab-avelumab-RT towards improving PFS, but the triplet was also associated with increased death without previous cancer progression in the first 6 months after RT. In the control arm, the doublet of cetuximab-RT regimen was better tolerated with no excess of death. Same good tolerance was also observed with doublet treatments in both arms of the PembroRad trial (NCT02707588). The addition of xevinapant to cetuximab is combining two complementary radiosensitizing effects that could ultimately improve the tumor control when compared to cetuximab alone. However, it is

Conditions

• Squamous Cell Carcinoma of the Head and Neck

Interventions

Type	Name	Description
DRUG	Xevinapant	Xevinapant is a multi-IAP antagonist that blocks the activity of several IAPs including X-linked IAP (XIAP), cellular inhibitor of apoptosis proteins (cIAP) 1, cIAP2 and ML-IAP
DRUG	Placebo	Xevinapant without active substance
DRUG	cetuximab	cetuximab
RADIATION	IMRT	IMRT (69.96 Gy in 33 fractions, 2.12 Gy/fraction)

Timeline

• Start date: 2023-12-12
• Primary completion: 2024-09-30
• Completion: 2024-09-30
• First posted: 2023-07-05
• Last updated: 2025-05-09

Locations

1 site across 1 country: France