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

NCT05724602 | Suspended Phase 2 DMC

• 2 other identifiers: EORTC 2120-HNCGEU trial Number
• Study Type: interventional
• Target: 230
• Locations: 10 countries
• Sites: 26

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

Keywords

Older adults (≥ 70 years)

Outcome Measures

Primary Outcomes (1)

• Locoregional event-free survival (LREFS)

  To demonstrate superior efficacy in terms of locoregional event-free survival of xevinapant vs placebo when added to radical radiotherapy in older patients with LA-HNSCC.

  5 years after first patient in

Secondary Outcomes (5)

• Response to treatment by RECIST 1.1

  5 years after first patient in

• Progression Free Survival as assessed by the local investigator

  5 years after first patient in

• Overall Survival

  5 years after first patient in

• Safety according to the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0 for toxicity and Serious Adverse Event reporting

  5 years after first patient in

• HRQOL as assessed by global health/QoL and physical functioning scales at week 20 (Fatigue scale from the Quality of Life Core-30 (QLQ-C30) and pain in the head and neck scale from Item List-225 (IL225)).

  5 years after first patient in

Study Arms (2)

Radiotherapy + Xevinapant

EXPERIMENTAL

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)

Drug: Xevinapant

Radiotherapy + Placebo

PLACEBO COMPARATOR

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).

Drug: Placebo

Interventions

Xevinapant DRUG

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

Radiotherapy + Xevinapant

Placebo DRUG

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

Radiotherapy + Placebo

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (26)

Onze Lieve Vrouw Ziekenhuis

Aalst, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, Belgium

Location

Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, Belgium

Location

Centre Oscar Lambret

Lille, France

Location

Institut de Cancerologie de Lorraine

Nancy, France

Location

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

Paris, France

Location

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

Paris, France

Location

Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum

Berlin, Germany

Location

Universitaetsklinikum - Essen

Essen, Germany

Location

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

Hamburg, Germany

Location

University Hospital Galway

Galway, Ireland

Location

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

Rathgar, Ireland

Location

IRCCS--Ospedale Bellaria-Bologna

Bologna, Italy

Location

Univ. of Florence -Azienda Ospedaliero-Universitaria Careggi

Florence, Italy

Location

Istituto Clinico Humanitas

Rozzano, Italy

Location

Amsterdam UMC - locatie VUMC

Amsterdam, Netherlands

Location

Universitair Medisch Centrum Groningen - University Medical Center Groningen

Groningen, Netherlands

Location

Academisch Ziekenhuis Maastricht

Maastricht, Netherlands

Location

Helse Bergen HF -Haukeland Hospital - Univ. Hosp

Bergen, Norway

Location

Oslo University Hospital - Radiumhospitalet

Oslo, Norway

Location

The Institute Of Oncology

Ljubljana, Slovenia

Location

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

Barcelona, Spain

Location

Vall D Hebron - Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

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

Birkenhead, United Kingdom

Location

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

Bristol, United Kingdom

Location

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

Glasgow, United Kingdom

Location

Study Officials

• Sjoukje Oosting, Dr

  University Medical Center Groningen

  STUDY CHAIR

• Pierluigi Bonomo, Dr

  Azienda Ospedaliero-Universitaria Careggi

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2023
• First Posted: February 13, 2023
• Study Start: November 15, 2023
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: August 27, 2024

Record last verified: 2024-08

Locations

IT (3); NL (3); BE (3); IE (2); FR (4); DE (3); SL (1); NO (2); GB (3); ES (2)