Study of Taxane-Platinum followed by a maintenance with avelumab and cetuximab in First Line Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck.

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

2 Jan 2025 → ongoing

Decision date (initial)

2024-11-12

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: Efficacy, Safety

To estimate the efficacy in terms of overall survival.

Secondary objectives 2

1. To estimate the efficacy in terms of Progression Free Survival (PFS).
2. To assess the safety of maintenance avelumab-cetuximab after PCC regimen

Conditions and MedDRA coding

Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Adult men and women ≥ 18 years and < 75 years.
2. Histologically confirmed recurrent and/or metastatic SCCHN (oral cavity, pharynx, larynx), not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy); squamous cell carcinoma of unknown primary if HPV positive.
3. Detection of PD-L1 protein expression in formalin-fixed, paraffin-embedded (FFPE) SCCHN tissue samples determined by Combined Positive Score (CPS) ≥1 using local IHC assay.
4. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
5. Patients without contra indication to PCC (either with cisplatin or carboplatin), to paclitaxel, cetuximab and to immunotherapy (avelumab).
6. Documentation of p16 status as surrogate of human papillomavirus (HPV) status of tumor for SCC of the oropharynx.
7. Measurable disease by CT or MRI per RECIST 1.1 criteria.
8. In case of radiotherapy given without systemic treatment, prior curative radiation therapy must have been completed at least 4 weeks before PCC administration and/or prior palliative radiotherapy must have been completed at least 2 weeks before PCC administration.
9. Screening laboratory values must meet the following criteria (using NCI-CTCAE v5) and should be obtained within 14 days prior to eligibility check: a. WBC > 2000/μL b. Polynuclear neutrophils >1.5 x 109/L c. Platelets > 100 x 109/L d. Hemoglobin > 9.0 g/dL e. ALAT/ASAT< 3.0 x ULN in the absence of liver metastases or < 5x ULN in the presence of liver metastases f. Bilirubin < 1.5 x ULN (except Gilbert Syndrome: < 3.0 mg/dL) g. Creatinine clearance > 60 mL/min (measured or calculated by preferably Cockcroft and Gault formula) for cisplatin administration and creatinine clearance ≥ 40 mL/min (measured or calculated by preferably Cockcroft and Gault formula) for carboplatin administration.
10. Calcium levels must be normalized and maintained within normal limits for study entry. Medical management of calcium levels is permitted. Note: Normal calcium levels may be based on ionized calcium or adjusted for albumin.

Exclusion criteria 8

1. Prior systemic chemotherapy for the head and neck carcinoma, except if given as part of a multimodal treatment for locally advanced disease which was completed more than 6 months prior to study entry.
2. Histologically confirmed recurrent or metastatic carcinomas of the nasopharynx, squamous cell carcinoma of unknown HPV negative primary, or salivary gland or non-squamous histologies (e.g., mucosal melanoma) are not allowed.
3. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
4. Prior malignancy active within the previous 3 years except for head and neck cancers and locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
5. Subjects with active, known or suspected autoimmune disease. Subjects with stabilized type I diabetes mellitus under treatment, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
6. Subjects with a condition requiring systemic chronic administration of corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of eligibility check. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
7. Patients having received prior therapy with anti-PD1, anti-PD-L1(or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
8. Prior anti-EGFR treatment received less than 6 months before eligibility check.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS) defined as the time between inclusion and death from any cause or the last follow-up contact for patients who are alive.

Secondary endpoints 2

1. Progression free survival (PFS) defined as the time between inclusion and first progression according to RECIST 1.1.
2. Incidence and severity of adverse events and serious adverse events during maintenance by the combination of cetuximab and avelumab and until 3 months after the last administration of maintenance (or until the start of a second line treatment if it starts before 3 months) as graded by the NCI Common Terminology Criteria of Adverse Events (NCI-CTCAE) v 5.0.

Investigational products

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

Test 2

Auxiliary 4

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

Dr Caroline EVEN

Public contact point

Organisation

Groupe Oncologie Radiotherapie Tete Cou

Contact name

Adeline PECHERY

Locations

1 EU/EEA country · 25 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

Urgent safety measures 1 · Art. 54 CTR

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 8 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