Trial Title:
Radiotherapy Plus Xevinapant in Older Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma
NCT ID:
NCT05724602
Condition:
Locally Advanced Head and Neck Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Conditions: Keywords:
Older adults (≥ 70 years)
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Suspended
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention:
Intervention type:
Drug
Intervention name:
Xevinapant
Description:
3 cycles of xevinapant + IMRT followed by 3 cycles of xevinapant as monotherapy
Arm group label:
Radiotherapy + Xevinapant
Intervention type:
Drug
Intervention name:
Placebo
Description:
3 cycles of placebo + IMRT followed by 3 cycles of placebo as monotherapy
Arm group label:
Radiotherapy + Placebo
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.
Criteria for eligibility:
Criteria:
Main 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.
Main 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.
Gender:
All
Minimum age:
70 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Onze Lieve Vrouw Ziekenhuis
Address:
City:
Aalst
Country:
Belgium
Facility:
Name:
Universitair Ziekenhuis Gent
Address:
City:
Gent
Country:
Belgium
Facility:
Name:
Cliniques Universitaires Saint-Luc
Address:
City:
Woluwe-Saint-Lambert
Country:
Belgium
Facility:
Name:
Centre Oscar Lambret
Address:
City:
Lille
Country:
France
Facility:
Name:
Institut de Cancerologie de Lorraine
Address:
City:
Nancy
Country:
France
Facility:
Name:
Assistance Publique Hopitaux Paris- APHP - APHP Sorbonne Univ - Hopital la Pitie-Salpetriere
Address:
City:
Paris
Country:
France
Facility:
Name:
Assistance Publique Hopitaux Paris- APHP - APHP Sorbonne Univ - Hopital Tenon
Address:
City:
Paris
Country:
France
Facility:
Name:
Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum
Address:
City:
Berlin
Country:
Germany
Facility:
Name:
Universitaetsklinikum - Essen
Address:
City:
Essen
Country:
Germany
Facility:
Name:
Universitaets Krankenhaus Eppendorf - Universitaetsklinikum Hamburg-Eppendorf KE - University Cancer Center
Address:
City:
Hamburg
Country:
Germany
Facility:
Name:
University Hospital Galway
Address:
City:
Galway
Country:
Ireland
Facility:
Name:
St Luke Hospital & SLRON - SLRON - St. Luke'S Hospital Rathgar
Address:
City:
Rathgar
Country:
Ireland
Facility:
Name:
IRCCS--Ospedale Bellaria-Bologna
Address:
City:
Bologna
Country:
Italy
Facility:
Name:
Univ. of Florence -Azienda Ospedaliero-Universitaria Careggi
Address:
City:
Florence
Country:
Italy
Facility:
Name:
Istituto Clinico Humanitas
Address:
City:
Rozzano
Country:
Italy
Facility:
Name:
Amsterdam UMC - locatie VUMC
Address:
City:
Amsterdam
Country:
Netherlands
Facility:
Name:
Universitair Medisch Centrum Groningen - University Medical Center Groningen
Address:
City:
Groningen
Country:
Netherlands
Facility:
Name:
Academisch Ziekenhuis Maastricht
Address:
City:
Maastricht
Country:
Netherlands
Facility:
Name:
Helse Bergen HF -Haukeland Hospital - Univ. Hosp
Address:
City:
Bergen
Country:
Norway
Facility:
Name:
Oslo University Hospital - Radiumhospitalet
Address:
City:
Oslo
Country:
Norway
Facility:
Name:
The Institute Of Oncology
Address:
City:
Ljubljana
Country:
Slovenia
Facility:
Name:
Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals
Address:
City:
Barcelona
Country:
Spain
Facility:
Name:
Vall D Hebron - Hospital Universitari Vall d'Hebron
Address:
City:
Barcelona
Country:
Spain
Facility:
Name:
The Clatterbridge cancer Center NHS foundation Trust - Clatterbridge Cancer Center - Wirral
Address:
City:
Birkenhead
Country:
United Kingdom
Facility:
Name:
University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre
Address:
City:
Bristol
Country:
United Kingdom
Facility:
Name:
NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital
Address:
City:
Glasgow
Country:
United Kingdom
Start date:
November 15, 2023
Completion date:
October 2029
Lead sponsor:
Agency:
European Organisation for Research and Treatment of Cancer - EORTC
Agency class:
Other
Collaborator:
Agency:
Merck KGaA, Darmstadt, Germany
Agency class:
Industry
Source:
European Organisation for Research and Treatment of Cancer - EORTC
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05724602
