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

Locally Advanced Head and Neck Squamous Cell Carcinoma Clinical Trial

— RAVINA  

Official title:

Radiotherapy Plus Xevinapant or Placebo in Older Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma: a Randomized Phase II Study RAVINA

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
• 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
• 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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Locally Advanced Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

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