Randomized trial of avelumab-cetuximab-Radiotherapy versus standards of care in the head and neck cancers

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] - Neoplasms [C04]

Trial duration

14 Sep 2017 → ongoing

Decision date (initial)

2024-09-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513964-24-00

EudraCT number

2016-004383-19

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To demonstrate that treatment with avelumab in combination with cetuximab-RT is superior to SOC cisplatin-RT and/or to SOC cetuximab-RT alone in terms of PFS in front-line patients with locally advanced SCCHN. Each cohort will be analyzed separately.

Secondary objectives 5

1. To compare the overall survival (OS), local regional control, distant metastases of avelumab in combination with cetuximab-RT vs SOC cisplatin-RT or SOC cetuximab-RT alone.
2. To evaluate the overall safety and tolerability profile of avelumab in combination with cetuximab-RT as compared to SOC cisplatin-RT or cetuximab-RT alone.
3. To evaluate the effect of avelumab in combination with cetuximab-RT compared to SOC CT-RT or cetuximab-RT alone on health-related quality of life.
4. To evaluate candidate immune-related predictive biomarkers of sensitivity or insensitivity to treatment with avelumab in pre-treatment tumor samples and in blood (levels of cells, DNA, RNA, or proteins that may be related to antitumor immune response and/or disease progression) and to explore potential correlations between treatment outcome and the immune landscape / TCR sequencing / antitumor cellular responses
5. To compare PFS2 (where events are progression on subsequent therapy after a first locoregional relapse or distant metastasis, or death of any cause) between patients randomized in the experimental arm avelumab-cetuximab-RT and patients randomized in the SOC arm in each cohort (i.e. cisplatin-RT for fit cohort and cetuximab-RT for unfit cohort)

Conditions and MedDRA coding

Squamous cell carcinoma, previously untreated Stage III, stage IVa (operable, but not operated) or IVb (non resectable) Oral cavity, oropharynx, hypopharynx or larynx

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age > 18 years and ≤ 80 years
2. Performance Status ECOG 0-1
3. Histologically confirmed squamous cell carcinoma, previously untreated
4. Stage III, stage IVa (i.e. operable, but not operated) or IVb (non resectable)
5. Oral cavity, oropharynx, hypopharynx or larynx
6. Determination of the patient’s ability to receive cisplatin 100 mg/m2 for 3 cycles (fit / unfit)** Criteria for determining if a patient is fit for receiving high dose cisplatin: - Calculated creatinine clearance ≥ 60 mL/min or glomerular filtration rate ≥ 60 mL/min/1.73m² (CKD-EPI method recommended), - Absolute neutrophil count ≥1 500/μL, platelets ≥100 000/μL, haemoglobin ≥ 10 g/dL, aspartate (AST) and alanine transaminase (ALT) less than 2 times the upper limit of the normal range (ULN), total bilirubin ≤ 1.5 mg/dL, serum albumin ≥ 35 g/L. - Peripheral neuropathy < grade 2 - No sensorineural hearing loss (confirmed by audiogram) - Cardiac function compatible with hyperhydration with no significant heart disease - No administration of prophylactic phenytoin - Age < 75 years. For patients aged 71-74 years, PS must be 0 and fit according to geriatric evaluation - General clinical state compatible with high dose cisplatin and radiotherapy according to the investigator

Exclusion criteria 11

1. Nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers
2. Squamous cell carcinoma involving cervical neck nodes with unknown primary site
3. Metastatic disease (stage IVc)
4. Active viral infection (HIV, Hepatitis B/C) or known history of positive test for HIV
5. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
6. Active immunodeficiency or ongoing immunosuppressive therapy
7. Interstitial lung disease
8. Active infection
9. Any prior or current treatment for invasive head and neck cancer. This will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, induction chemotherapy, prior surgical resection or RT, or use of any investigational agent. Minor surgery in the head and neck area (e.i. dental extraction diagnostic biopsy) are authorized if performed more than 1 week before study entry and under condition of wound healing.
10. Concomitant treatment with any drug on the prohibited medication list such as live vaccines or systemic corticoids at dose > 10 mg/day prednisone or equivalent. Live vaccines administered more than 30 days before study entry are permitted.
11. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS defined as the time between randomization and the first event among progression (per radiologico-pathological combined Head & Neck cancer assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 (see Appendix) and death, whatever the cause of death

Secondary endpoints 5

1. Overall survival
2. Cumulative incidence of locoregional failure, cumulative incidence of distant metastatic failure by Investigator assessment (Appendix 3) and cumulative incidence of death without previous progression
3. Safety: Acute adverse events and laboratory abnormalities as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), v4.03. Incidence of delayed toxicity (e.g.; dysphagia, chronic swallowing dysfunctions, speech problems, cervical fibrosis, rate and duration of the use of feeding tubes);
4. Patient-Reported Outcomes: Health related quality of life (QL) assessed by EORTC QLQC30 and H&N35 questionnaires
5. Progression Free Survival 2 (PFS2) defined as the time from randomization to progression on subsequent treatment for logoregional relapse, distant metastasis or detah from any cause

Investigational products

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

Test 2

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Groupe Oncologie Radiotherapie Tete Cou

Sponsor organisation

Groupe Oncologie Radiotherapie Tete Cou

Address

4 B Rue Emile Zola

City

Tours

Postcode

37000

Country

France

Scientific contact point

Organisation

Groupe Oncologie Radiotherapie Tete Cou

Contact name

Pr Jean BOURHIS

Public contact point

Organisation

Groupe Oncologie Radiotherapie Tete Cou

Contact name

Laura SINIGAGLIA

Locations

1 EU/EEA country · 51 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 13 files

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

Application history

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