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JOURNAL ONKOLOGIE – STUDIE
RAVINA

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

Rekrutierend

NCT-Nummer:
NCT05724602

Studienbeginn:
November 2023

Letztes Update:
22.02.2024

Wirkstoff:
Xevinapant, Placebo

Indikation (Clinical Trials):
Carcinoma, Carcinoma, Squamous Cell, Squamous Cell Carcinoma of Head and Neck

Geschlecht:
Alle

Altersgruppe:
Senioren (66+)

Phase:
Phase 2

Sponsor:
European Organisation for Research and Treatment of Cancer - EORTC

Collaborator:
Merck KGaA, Darmstadt, Germany

Studienleiter

Sjoukje Oosting, Dr
Study Chair
University Medical Center Groningen
Pierluigi Bonomo, Dr
Study Chair
Azienda Ospedaliero-Universitaria Careggi

Kontakt

Studienlocations
(3 von 26)

Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum
Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Universitaetsklinikum - Essen
Essen
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Universitaets Krankenhaus Eppendorf - Universitaetsklinikum Hamburg-Eppendorf KE - University Cancer Center
Hamburg
(Hamburg)
GermanyNoch nicht rekrutierend» Google-Maps
Cliniques Universitaires Saint-Luc
Woluwe-Saint-Lambert
BelgiumRekrutierend» Google-Maps
Assistance Publique Hopitaux Paris- APHP - APHP Sorbonne Univ - Hopital la Pitie-Salpetriere
Paris
FranceNoch nicht rekrutierend» Google-Maps
Assistance Publique Hopitaux Paris- APHP - APHP Sorbonne Univ - Hopital Tenon
Paris
FranceNoch nicht rekrutierend» Google-Maps
University Hospital Galway
Galway
IrelandNoch nicht rekrutierend» Google-Maps
St Luke Hospital & SLRON - SLRON - St. Luke'S Hospital Rathgar
Rathgar
IrelandNoch nicht rekrutierend» Google-Maps
IRCCS--Ospedale Bellaria-Bologna
Bologna
ItalyNoch nicht rekrutierend» Google-Maps
Univ. of Florence -Azienda Ospedaliero-Universitaria Careggi
Florence
ItalyNoch nicht rekrutierend» Google-Maps
Istituto Clinico Humanitas
Rozzano
ItalyNoch nicht rekrutierend» Google-Maps
Amsterdam UMC - locatie VUMC
Amsterdam
NetherlandsRekrutierend» Google-Maps
Universitair Medisch Centrum Groningen - University Medical Center Groningen
Groningen
NetherlandsRekrutierend» Google-Maps
Academisch Ziekenhuis Maastricht
Maastricht
NetherlandsNoch nicht rekrutierend» Google-Maps
Helse Bergen HF -Haukeland Hospital - Univ. Hosp
Bergen
NorwayNoch nicht rekrutierend» Google-Maps
Oslo University Hospital - Radiumhospitalet
Oslo
NorwayRekrutierend» Google-Maps
Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals
Barcelona
SpainRekrutierend» Google-Maps
Vall D Hebron - Hospital Universitari Vall d'Hebron
Barcelona
SpainNoch nicht rekrutierend» Google-Maps
The Clatterbridge cancer Center NHS foundation Trust - Clatterbridge Cancer Center - Wirral
Birkenhead
United KingdomNoch nicht rekrutierend» Google-Maps
University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre
Bristol
United KingdomNoch nicht rekrutierend» Google-Maps
NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital
Glasgow
United KingdomNoch nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

1. Locoregional event-free survival (LREFS) (Time Frame - 5 years after first patient in):
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.



Secondary outcome:

1. Response to treatment by RECIST 1.1 (Time Frame - 5 years after first patient in):
To estimate the added value of xevinapant over RT alone in terms of response to treatment.

2. Progression Free Survival as assessed by the local investigator (Time Frame - 5 years after first patient in):
To estimate the added value of xevinapant over RT alone in PFS.

3. Overall Survival (Time Frame - 5 years after first patient in):
To estimate the added value of xevinapant over RT alone in OS.

4. Safety according to the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0 for toxicity and Serious Adverse Event reporting (Time Frame - 5 years after first patient in):
To evaluate the frequency and severity of toxicities according to CTCAE v5.0 in the two arms.

5. 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)). (Time Frame - 5 years after first patient in):
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.

Studien-Arme

  • Experimental: Radiotherapy + Xevinapant
    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)
  • Placebo Comparator: Radiotherapy + Placebo
    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).

Geprüfte Regime

  • 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

Quelle: ClinicalTrials.gov


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