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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05724602
Other study ID # EORTC 2120-HNCG
Secondary ID EU trial Number
Status Recruiting
Phase Phase 2
First received
Last updated
Start date November 15, 2023
Est. completion date October 2029

Study information

Verified date April 2024
Source European Organisation for Research and Treatment of Cancer - EORTC
Contact EORTC HQ
Phone +32 2 774 16 11
Email eortc@eortc.org
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Recruiting
Enrollment 230
Est. completion date October 2029
Est. primary completion date July 2029
Accepts healthy volunteers No
Gender All
Age group 70 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Xevinapant
3 cycles of xevinapant + IMRT followed by 3 cycles of xevinapant as monotherapy
Placebo
3 cycles of placebo + IMRT followed by 3 cycles of placebo as monotherapy

Locations

Country Name City State
Belgium Onze Lieve Vrouw Ziekenhuis Aalst
Belgium Universitair Ziekenhuis Gent Gent
Belgium Cliniques Universitaires Saint-Luc Woluwe-Saint-Lambert
France 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
Germany Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum Berlin
Germany Universitaetsklinikum - Essen Essen
Germany Universitaets Krankenhaus Eppendorf - Universitaetsklinikum Hamburg-Eppendorf KE - University Cancer Center Hamburg
Ireland University Hospital Galway Galway
Ireland St Luke Hospital & SLRON - SLRON - St. Luke'S Hospital Rathgar Rathgar
Italy IRCCS--Ospedale Bellaria-Bologna Bologna
Italy Univ. of Florence -Azienda Ospedaliero-Universitaria Careggi Florence
Italy Istituto Clinico Humanitas Rozzano
Netherlands Amsterdam UMC - locatie VUMC Amsterdam
Netherlands Universitair Medisch Centrum Groningen - University Medical Center Groningen Groningen
Netherlands Academisch Ziekenhuis Maastricht Maastricht
Norway Helse Bergen HF -Haukeland Hospital - Univ. Hosp Bergen
Norway Oslo University Hospital - Radiumhospitalet Oslo
Slovenia The Institute Of Oncology Ljubljana
Spain Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals Barcelona
Spain Vall D Hebron - Hospital Universitari Vall d'Hebron Barcelona
United Kingdom 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

Sponsors (2)

Lead Sponsor Collaborator
European Organisation for Research and Treatment of Cancer - EORTC Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

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

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Response to treatment by RECIST 1.1 To estimate the added value of xevinapant over RT alone in terms of response to treatment. 5 years after first patient in
Secondary Progression Free Survival as assessed by the local investigator To estimate the added value of xevinapant over RT alone in PFS. 5 years after first patient in
Secondary Overall Survival To estimate the added value of xevinapant over RT alone in OS. 5 years after first patient in
Secondary Safety according to the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0 for toxicity and Serious Adverse Event reporting To evaluate the frequency and severity of toxicities according to CTCAE v5.0 in the two arms. 5 years after first patient in
Secondary 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)). To assess non-inferiority of xevinapant arm compared to placebo in terms of health-related quality of life (HRQoL) as assessed by the EORTC QLQ-C30 global health/QoL and physical functioning scales.
The questionnaires employ 50 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall HRQoL. For functional and global HRQoL scales, higher scores represent a better level of functioning and are converted to a 0 to 100 scale. For symptom-oriented scales, a higher score represents more severe symptoms.
5 years after first patient in
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