Radiotherapy plus xevinapant or placebo in older patients with locally advanced head and neck cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

European Organisation For Research And Treatment Of Cancer

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Otorhinolaryngologic Diseases [C09], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]

Trial duration

15 Nov 2023 → 11 Jun 2025

Decision date (initial)

2023-07-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

EUROPEAN ORGANISATION FOR RESEARCH AND TREATMENT OF CANCER · Merck Healthcare KGaA

External identifiers

EU CT number

2022-502339-20-00

ClinicalTrials.gov

NCT05724602

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Others

The primary objective is to assess the benefit of adding xevinapant to RT in terms of duration of locoregional event-free survival (LREFS) in older patients with LA-HNSCC

Secondary objectives 5

1. To estimate the added value of xevinapant over RT alone in terms of response to treatment according to RECIST
2. To estimate the added value of xevinapant over RT alone in PFS.
3. To estimate the added value of xevinapant over RT alone in OS.
4. To evaluate the frequency and severity of toxicities according to CTCAE v5.0 in the two arms.
5. To assess non-inferiority of xevinapant 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 fatigue scale from the QLQ-C30, and pain in the head and neck scale from IL225 will also be assessed to provide additional insight into the treatment effects for the global health/QOL scale (QLQ-C30) and the physical functioning scales.

Conditions and MedDRA coding

Squamous cell carcinoma of head and neck

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Age ≥ 70 years.
2. Pathologically proven new diagnosis of HNSCC of oral cavity, oropharynx, hypopharynx and larynx tumour.
3. cT3-4 cN0 cM0 or cT1-4 cN1-3 cM0 except for cT1-2 cN1 p16 positive oropharyngeal cancer (AJCC 8th edition).
4. HPV status using p16 immunohistochemistry (IHC) available for oropharyngeal squamous cell carcinoma.
5. Measurable disease per RECIST 1.1.
6. ECOG PS ≤ 1.
7. Intention to treat with curative intent primary radiotherapy alone.
8. Able to swallow liquids or has an adequately functioning feeding tube, gastrostomy or jejunostomy placed.
9. 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).
10. Written informed consent must be signed according to ICH/GCP, and national/local regulations

Exclusion criteria 10

1. Unknown primary, primary nasopharynx and paranasal sinus
2. Two primaries.
3. Any previous or current treatment for invasive head and neck cancer, including induction chemotherapy, surgery, concomitant chemotherapy and cetuximab.
4. Gastrointestinal disorders that could affect drug absorption.
5. Another malignancy in the previous 3 years with exception of curatively treated disease with no evidence of recurrence.
6. Known allergy to xevinapant or any excipient known to be present in active or placebo formulation.
7. 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
8. Decompensated or symptomatic liver cirrhosis (Child-Pugh score: B or C)
9. Impaired cardiovascular function or clinically significant cardiovascular diseases
10. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is locoregional event-free survival (LREFS) as assessed by the local investigator. Events are defined as locoregional progression, recurrence of locoregional disease, new SCC of the head and neck in the radiation field and death from any cause.

Secondary endpoints 5

1. Response to treatment according to RECIST 1.1
2. Progression Free Survival as assessed by the local investigator.
3. Overall Survival
4. Safety according to the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0 for toxicity and Serious Adverse Event reporting
5. Patient-reported HRQoL as assessed by global health/QoL and physical functioning scales from the EORTC QLQ-C30 at week 20. The fatigue scale from the QLQ-C30, and pain in the head and neck scale from IL225 will be assessed to provide additional insight into the treatment effects for the global health/QOL scale (QLQ-C30) and the physical functioning scales

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

European Organisation For Research And Treatment Of Cancer

Sponsor organisation

European Organisation For Research And Treatment Of Cancer

Address

Emmanuel Mounierlaan 83/11

City

Sint-Lambrechts-Woluwe

Postcode

1200

Country

Belgium

Scientific contact point

Organisation

European Organisation For Research And Treatment Of Cancer

Contact name

Stéphanie Kromar

Public contact point

Organisation

European Organisation For Research And Treatment Of Cancer

Contact name

Vassilis Golfinopoulos

Third parties 2

Locations

9 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 8 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications