Radiotherapy Plus Xevinapant in Older Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma

NCT ID: NCT05724602

Last Updated: 2024-08-27

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE2
• Total Enrollment: 230 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-15
• Study Completion Date: 2029-10-31

Brief Summary

This is a multicenter, randomized, placebo-controlled, triple blind, phase II study to determine the efficacy and safety of xevinapant with radiotherapy in older patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) of oral cavity, oropharynx, hypopharynx, or larynx.

Upon confirmation of eligibility, subjects will be enrolled and randomized in a 1:1 ratio to:

• Arm A: 3 cycles of xevinapant (200 mg/day from Day 1 to 14, per cycle) + intensive modulated radiotherapy (IMRT) followed by 3 cycles of xevinapant in monotherapy phase (200 mg/day from Day 1 to 14, per cycle)
• Arm B: 3 cycles of placebo (from Day 1 to 14, per cycle) + IMRT followed by 3 cycles of placebo in monotherapy phase (from Day 1 to 14, per cycle).

Patients will be stratified by institution, disease location/p16 status (p16 positive oropharyngeal cancer, versus others), G8 score. Three strata for the G8 will be used (>14, versus 11-14 versus <11).

Patients will undergo imaging in week 20 and upon clinical suspicion of progression/recurrence. Clinical examination will take place every 12 weeks in the first 3 years.

Conditions

Locally Advanced Head and Neck Squamous Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Radiotherapy + Xevinapant

3 cycles of xevinapant (200 mg/day from Day 1 to 14, per 21-day cycle) + IMRT followed by 3 cycles of xevinapant in monotherapy (200 mg/day from Day 1 to 14, per 21-day cycle)

Group Type: EXPERIMENTAL

Xevinapant

Intervention Type: DRUG

3 cycles of xevinapant + IMRT followed by 3 cycles of xevinapant as monotherapy

Radiotherapy + Placebo

3 cycles of placebo (from Day 1 to 14, per 21-day cycle) + IMRT followed by 3 cycles of placebo in monotherapy (from Day 1 to 14, per 21-day cycle).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

3 cycles of placebo + IMRT followed by 3 cycles of placebo as monotherapy

Interventions

Xevinapant

3 cycles of xevinapant + IMRT followed by 3 cycles of xevinapant as monotherapy

Intervention Type: DRUG

Placebo

3 cycles of placebo + IMRT followed by 3 cycles of placebo as monotherapy

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age ≥ 70 years.
• Pathologically proven new diagnosis of HNSCC of oral cavity, oropharynx, hypopharynx and larynx tumor.
• cT3-4 cN0 cM0 or cT1-4 cN1-3 cM0 except for T1-2N1 p16 positive oropharyngeal cancer (AJCC 8th edition).
• HPV status using p16 immunohistochemistry (IHC) available for oropharyngeal squamous cell carcinoma.
• Measurable disease per RECIST 1.1.
• Eastern Coperative Oncology Group Performance Status (ECOG PS) ≤ 1.
• Intention to treat with curative intent primary radiotherapy alone.
• Able to swallow liquids or has an adequately functioning feeding tube, gastrostomy or jejunostomy placed.
• Adequate hematologic, renal, and hepatic function as indicated by:
• Creatinine clearance ≥ 30 mL/min, measured with the Cockroft and Gault formula.
• Absolute neutrophil count ≥ 1 500 cells/μL.
• Platelets ≥ 100 000 cells/μL.
• Hemoglobin ≥ 9.0 g/dL or ≥5.6 mmol/L (blood transfusions during screening are permitted).
• AST and ALT ≤ 3.0 × upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 × ULN (up to 2.0 × ULN is allowed if the direct bilirubin level is normal and the elevation is limited to indirect bilirubin).
• Written informed consent must be signed according to ICH/GCP, and national/local regulations.

Exclusion Criteria

• Unknown primary, primary nasopharynx and paranasal sinus.
• Two primaries.
• Any previous or current treatment for invasive head and neck cancer, including induction chemotherapy, surgery, concomitant chemotherapy and cetuximab.
• Gastrointestinal disorders that could affect drug absorption.
• Another malignancy in the previous 3 years with exception of curatively treated disease with no evidence of recurrence.
• Known allergy to xevinapant or any excipient known to be present in active or placebo formulation.
• Active gastrointestinal bleeding, or any other uncontrolled bleeding requiring more than 2 red blood cell transfusions or 4 units of packed red blood cells within 4 weeks prior to enrolment
• Non-Decompensated or symptomatic liver cirrhosis (Child-Pugh score: B or C).
• Impaired cardiovascular function or clinically significant cardiovascular diseases
• Any uncontrolled, intercurrent illness or clinical situation that would in the judgment of investigator, limit compliance with study requirements. This includes but is not limited to uncontrolled active infections, defined as any infection requiring IV antibiotics within 7 days prior to enrolment.

• Minimum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sjoukje Oosting, Dr

Role: STUDY_CHAIR

University Medical Center Groningen

Pierluigi Bonomo, Dr

Role: STUDY_CHAIR

Azienda Ospedaliero-Universitaria Careggi

Locations

Onze Lieve Vrouw Ziekenhuis

Aalst, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, , Belgium

Centre Oscar Lambret

Lille, , France

Institut de Cancerologie de Lorraine

Nancy, , France

Assistance Publique Hopitaux Paris- APHP - APHP Sorbonne Univ - Hopital la Pitie-Salpetriere

Paris, , France

Assistance Publique Hopitaux Paris- APHP - APHP Sorbonne Univ - Hopital Tenon

Paris, , France

Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum

Berlin, , Germany

Universitaetsklinikum - Essen

Essen, , Germany

Universitaets Krankenhaus Eppendorf - Universitaetsklinikum Hamburg-Eppendorf KE - University Cancer Center

Hamburg, , Germany

University Hospital Galway

Galway, , Ireland

St Luke Hospital & SLRON - SLRON - St. Luke'S Hospital Rathgar

Rathgar, , Ireland

IRCCS--Ospedale Bellaria-Bologna

Bologna, , Italy

Univ. of Florence -Azienda Ospedaliero-Universitaria Careggi

Florence, , Italy

Istituto Clinico Humanitas

Rozzano, , Italy

Amsterdam UMC - locatie VUMC

Amsterdam, , Netherlands

Universitair Medisch Centrum Groningen - University Medical Center Groningen

Groningen, , Netherlands

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

Helse Bergen HF -Haukeland Hospital - Univ. Hosp

Bergen, , Norway

Oslo University Hospital - Radiumhospitalet

Oslo, , Norway

The Institute Of Oncology

Ljubljana, , Slovenia

Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals

Barcelona, , Spain

Vall D Hebron - Hospital Universitari Vall d'Hebron

Barcelona, , Spain

The Clatterbridge cancer Center NHS foundation Trust - Clatterbridge Cancer Center - Wirral

Birkenhead, , United Kingdom

University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre

Bristol, , United Kingdom

NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital

Glasgow, , United Kingdom

Countries

Belgium; France; Germany; Ireland; Italy; Netherlands; Norway; Slovenia; Spain; United Kingdom

Other Identifiers

EU trial Number

Identifier Type: OTHER

Identifier Source: secondary_id

EORTC 2120-HNCG

Identifier Type: -

Identifier Source: org_study_id