Locally Advanced Head and Neck Squamous Cell CarcinomaPhase 2RAVINANCT05724602
Radiotherapy Plus Xevinapant in Older Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma
A Phase 2 study testing Xevinapant in people with Locally Advanced Head and Neck Squamous Cell Carcinoma, run by European Organisation for Research and Treatment of Cancer - EORTC at 26 sites in 10 countries.
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. Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Locally Advanced Head and Neck Squamous Cell Carcinoma
- What is being tested?
- Xevinapant
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 26 sitesin 10 countries
- Study dates
- 15 Nov 2023to 17 Feb 2025
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 years and older
- All sexes
- No healthy volunteers
- Older adult
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.
Trial locations and contacts
26 sites in 10 countries.
26 sites in 10 countries
France4 sites
Centre Oscar Lambret
Lille
Institut de Cancerologie de Lorraine
Nancy
Assistance Publique Hopitaux Paris- APHP - APHP Sorbonne Univ - Hopital la Pitie-Salpetriere
Paris
Assistance Publique Hopitaux Paris- APHP - APHP Sorbonne Univ - Hopital Tenon
Paris
Belgium3 sites
Onze Lieve Vrouw Ziekenhuis
Aalst
Universitair Ziekenhuis Gent
Ghent
Cliniques Universitaires Saint-Luc
Woluwe-Saint-Lambert
Germany3 sites
Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum
Berlin
Universitaetsklinikum - Essen
Essen
Universitaets Krankenhaus Eppendorf - Universitaetsklinikum Hamburg-Eppendorf KE - University Cancer Center
Hamburg
Italy3 sites
IRCCS--Ospedale Bellaria-Bologna
Bologna
Univ. of Florence -Azienda Ospedaliero-Universitaria Careggi
Florence
Istituto Clinico Humanitas
Rozzano
Netherlands3 sites
Amsterdam UMC - locatie VUMC
Amsterdam
Universitair Medisch Centrum Groningen - University Medical Center Groningen
Groningen
Academisch Ziekenhuis Maastricht
Maastricht
United Kingdom3 sites
The Clatterbridge cancer Center NHS foundation Trust - Clatterbridge Cancer Center - Wirral
Birkenhead
University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre
Bristol
NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital
Glasgow
Ireland2 sites
University Hospital Galway
Galway
St Luke Hospital & SLRON - SLRON - St. Luke'S Hospital Rathgar
Rathgar
Norway2 sites
Helse Bergen HF -Haukeland Hospital - Univ. Hosp
Bergen
Oslo University Hospital - Radiumhospitalet
Oslo
Spain2 sites
Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals
Barcelona
Vall D Hebron - Hospital Universitari Vall d'Hebron
Barcelona
About this study
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
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:
Read more
- 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.
- Being tested
- Xevinapant, Placebo
- Keywords
- Older adults (≥ 70 years)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XevinapantDrug
3 cycles of xevinapant + IMRT followed by 3 cycles of xevinapant as monotherapy
PlaceboDrug
3 cycles of placebo + IMRT followed by 3 cycles of placebo as monotherapy
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 years after first patient in
Secondary outcomes (5)
Response to treatment by RECIST 1.1
To estimate the added value of xevinapant over RT alone in terms of response to treatment.
Measured: 5 years after first patient in
Progression Free Survival as assessed by the local investigator
To estimate the added value of xevinapant over RT alone in PFS.
Measured: 5 years after first patient in
Overall Survival
To estimate the added value of xevinapant over RT alone in OS.
Measured: 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
To evaluate the frequency and severity of toxicities according to CTCAE v5.0 in the two arms.
Measured: 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)).
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.
Measured: 5 years after first patient in
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2023
- Study start15 Nov 2023
- Primary completion17 Feb 2025
- Study completion17 Feb 2025
Why it stopped: discontinuation of all ongoing studies involving xevinapant
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Sjoukje Oosting, Dr, Study chair, University Medical Center GroningenPierluigi Bonomo, Dr, Study chair, Azienda Ospedaliero-Universitaria Careggi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05724602
- Sponsor's protocol ID
- EORTC 2120-HNCG
- Other IDs
- EU trial Number
- Acronym
- RAVINA
- Status last verified
- Aug 2026
- First submitted
- 17 Jan 2023
- Last updated
- 20 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No