Study comparing radiotherapy combined with cetuximab + Xevinapant (study drug) with radiotherapy combined with cetuximab + placebo in patients with head and neck cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Groupe Oncologie Radiotherapie Tete Cou

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23], Diseases [C] - Neoplasms [C04]

Trial duration

12 Dec 2023 → 30 Sep 2024

Decision date (initial)

2023-08-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Pharmacogenomic, Efficacy

To demonstrate improvement in PFS evaluated by an independent review committee (IRC) with xevinapant-cetuximab-RT compared to placebo-cetuximab-RT

Secondary objectives 4

1. To demonstrate improvement in OS with xevinapant-cetuximab-RT compared to placebo-cetuximab-RT (main secondary objective)
2. To demonstrate improvement in PFS as evaluated by local investigator with xevinapant-cetuximab-RT compared to placebo-cetuximab-RT
3. To evaluate the treatment compliance of xevinapant-cetuximab-RT compared to placebo-cetuximab-RT
4. To evaluate the safety and tolerability of xevinapant-cetuximab-RT compared to placebo-cetuximab-RT

Conditions and MedDRA coding

Locally advanced squamous cell carcinoma of the head and neck

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Male or Female ≥ 18 years (or based on the country legal age limit for adults on day of signing the Informed Consent Form, ICF) and < 80 years
2. ECOG PS 0-1
3. Histologically confirmed diagnosis in previously untreated LA-SCCHN participant (Stage III, IVA or IVB according to the American Joint Committee on Cancer [AJCC]/TNM Staging System, 8th Ed.) of at least one of the following sites: oral cavity, hypopharynx and larynx. OPC participants are also eligible but their primary tumor must be: • HPV-negative (Stage III, IVA or IVB according to the American Joint Committee on Cancer [AJCC]/TNM Staging System, 8th Ed.) or • HPV-positive and smokers > 20 PY and must have according to the American Joint Committee on Cancer [AJCC]/TNM Staging System, 8th Ed: o T3 N1-3 o T4 and any N
4. Able to swallow liquids or have an adequately functioning feeding tube, gastrostomy or jejunostomy placed.
5. Patients must be ineligible to receive high-dose cisplatin defined as ≥ 200 mg/m² (projected total cumulative dose throughout the course of the RT). Ineligibility is defined as at least one of the following criteria: • eGFR < 60 mL/min /1.73 m² (using the CKD-EPI creatinine formula) • History of hearing loss, defined as either: i. Existing need of a hearing aid and/or ii. Clinically relevant hearing loss by clinical assessment including tinnitus ≥ Grade 2. Note: In case of doubt, an audiogram should be requested to guide the Investigator • Peripheral neuropathy ≥ Grade 2 • Cardiac function not compatible with hyperhydration • If > 70 years, unfit according to G8 questionnaire (Score ≤ 14)
6. Adequate hematologic, renal and hepatic function as indicated by (using CTCAE v5.0): • Absolute neutrophil count ≥ 1500 /mm3 • Platelets ≥ 100 000 /mm3 • Hemoglobin ≥ 9.0 g/dL (blood transfusions during Screening are not permitted) • White blood cells ≥ 3 000/mm3 • AST and ALT ≤ 3 × ULN • eGFR ≥ 30 mL/min /1.73 m² (using the CKD-EPI creatinine formula) • 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)
7. The Investigator confirms that the participant agrees to use appropriate contraception and barriers methods, if applicable
8. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the inform consent form and this protocol

Exclusion criteria 12

1. Any condition, including any uncontrolled disease state other than SCCHN that in the Investigator’s opinion constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation.
2. Metastatic disease (according to AJCC/TNM, 8th ed.).
3. Primary tumor of nasopharyngeal, paranasal sinuses, salivary, thyroid or parathyroid gland, skin or unknown primary site.
4. Known gastrointestinal disorder with clinically established malabsorption syndrome and major gastrointestinal surgery that may limit oral absorption
5. Documented weight loss of > 10% during the last 4 weeks prior to randomization (unless adequate measures are undertaken for nutritional support), OR plasmatic albumin < 3.0 g/dL. No albumin transfusions are allowed within 2 weeks before randomization.
6. 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 randomization.
7. Active uncontrolled inflammatory disease (including rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, severe extensive psoriasis, and other autoimmune diseases) requiring ongoing treatment with anti-TNF medication.
8. Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following
9. Hypertension uncontrolled by medication (i.e. systolic blood pressure > 150 mmHg and diastolic blood pressure > 90 mmHg).
10. Symptomatic pulmonary disease requiring continuous or intermittent oxygen supply.
11. History of another malignancy within the last 3 years prior to randomization, with the exception of completely resected non-melanoma cell skin cancer outside the head and neck area or completely resected stage I breast cancer, or completely resected in-situ non-muscular invasive bladder, cervix and/or uterine carcinomas.
12. Non compensated or symptomatic liver cirrhosis (Child-Pugh score: B or C).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS as assessed by independent review committee (IRC) defined as the time from randomization to the first occurrence of any of the following events: death from any cause, disease progression (PD), primary treatment failure before achieving a complete response (CR) or any radiological or clinical relapse after achieving a CR

Secondary endpoints 4

1. OS, main secondary endpoint, defined as the time from date of randomization to the date of death. Patients last known to be alive will be censored at date of last contact.
2. Progression-free survival by investigator assessment.
3. Compliance will be reported: for radiotherapy (tumor dose, number of fractions, duration and major deviations), for xevinapant/placebo, cetuximab (number of cycles, dose, duration, dose intensity and relative dose intensity). Whatever the treatment, treatment interruption, reduction and discontinuation and their reasons will be reported
4. Occurrence of adverse events (AEs) and treatment-related AEs.

Investigational products

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

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Groupe Oncologie Radiotherapie Tete Cou

Sponsor organisation

Groupe Oncologie Radiotherapie Tete Cou

Address

2 Boulevard Tonnelle

City

Tours

Postcode

37000

Country

France

Scientific contact point

Organisation

Groupe Oncologie Radiotherapie Tete Cou

Contact name

Cordinating investigator

Public contact point

Organisation

Groupe Oncologie Radiotherapie Tete Cou

Contact name

Porject manager

Locations

1 EU/EEA country · 28 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 1 · Art. 38 CTR

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

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

Application history

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