Study of TPEx Followed by a Maintenance With Avelumab and Cetuximab in First Line Recurrent or Metastatic Squamous Cell Carcinoma of the H&N

NCT06640725 | Recruiting Phase 2

• 2 other identifiers: GORTEC 2024-012023-510559-41-00
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of this research is to increase the life expectancy of patients with advanced mouth and throat cancer, by adding avelumab to the standard TPEx treatment. All participants in this research will receive the same treatment which will take place in two phases:

• 1st phase chemotherapy + immunotherapy: standard reference treatment (Docetaxel + cisplatin or carboplatin + cetuximab)
• 2nd phase immunotherapy: cetuximab combined with avelumab which is the treatment under study.

Conditions

Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival (OS) defined as the time from the inclusion in the study to death due to any cause or the last follow-up contact for patients who are alive.

  1, 2and 3 years

Study Arms (1)

TPEx-Avelumab-Cetuximab

EXPERIMENTAL

Induction (TPEx regimen: up to 4 cycles Q3W) Cisplatin 75 mg/m² or Carboplatin AUC 5 every 3 weeks (±2 days). Docetaxel 75 mg/m² every 3 weeks (±2 days). Cetuximab with a loading dose of 400mg/m² at C1D1 and after 250mg/m² every week (±2 days). Cetuximab 500 mg/m² every 2 weeks (±3 days) (according to current recommendations \[35\]) Avelumab 10 mg/kg every 2 weeks (±3 days)

Drug: Avelumab administration at 10mg/kg; Drug: Cetuximab (Erbitux)

Interventions

Avelumab administration at 10mg/kg DRUG

Maintenance (until progression, unacceptable toxicity or if CR \> 1 year, as per investigator choice) Avelumab 10 mg/kg every 2 weeks (±3 days)

TPEx-Avelumab-Cetuximab

Cetuximab (Erbitux) DRUG

Maintenance (until progression, unacceptable toxicity or if CR \> 1 year, as per investigator choice) Cetuximab 500 mg/m² every 2 weeks (±3 days) (according to current recommendations \[35\])

TPEx-Avelumab-Cetuximab

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult men and women ≥ 18 years and \< 75 years.
• 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.
• 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.
• Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Patients without contra indication to TPEx (either with cisplatin or carboplatin), to docetaxel, cetuximab and to immunotherapy (avelumab).Investigators must refer to the last updated version of Summary of product Characteristics (SPC) of the products.
• Documentation of p16 status as surrogate of human papillomavirus (HPV) status of tumor for SCC of the oropharynx.
• Measurable disease by CT or MRI per RECIST 1.1 criteria.
• In case of radiotherapy given without systemic treatment, prior curative radiation therapy must have been completed at least 4 weeks before TPEx administration and/or prior palliative radiotherapy must have been completed at least 2 weeks before TPEx administration.
• Screening laboratory values must meet the following criteria (using NCI-CTCAE v5) and should be obtained within 14 days prior to eligibility check:
• WBC \> 2000/μL
• Polynuclear neutrophils \>1.5 x 109/L
• Platelets \> 100 x 109/L
• Hemoglobin \> 9.0 g/mL
• ALAT/ASAT\< 3.0 x ULN in the absence of liver metastases or \< 5x ULN in the presence of liver metastases
• Bilirubin \< 1.5 x ULN (except Gilbert Syndrome: \< 3.0 mg/dL)

You may not qualify if:

• 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.
• 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.
• 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.
• Prior malignancy active within the previous 3 years except for 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.
• 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.
• 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.
• 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).
• Prior anti-EGFR treatment received less than 6 months before eligibility check.
• Patients with known positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Patients with known positive tests for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection.
• Use of non-oncology vaccines containing live virus or bacteria for prevention of infectious diseases within 4 weeks prior to eligibility check. The use of the inactivated seasonal influenza vaccine is allowed.
• History of severe hypersensitivity reaction to any human monoclonal antibody.
• Severe concurrent psychiatric conditions that would limit compliance with study requirements.
• Serious systemic infection requiring hospital treatment with intravenous antibiotics within 14 days prior eligibility check.
• History of organ transplant. 16.Patients presenting hemorrhagic tumor, only if carboplatin is administrated. 17.Concomitant phenytoin and fosphenytoin medication during the study treatment period.

Sponsors & Collaborators

• Groupe Oncologie Radiotherapie Tete et Cou: lead

Study Sites (1)

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54519, France

RECRUITING

MeSH Terms

Conditions

Recurrence

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Caroline EVEN, MD

CONTACT

0142116597; caroline.even@gustaveroussy.fr

Adeline PECHERY

CONTACT

0649210607; adeline.pechery@gortec.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2024
• First Posted: October 15, 2024
• Study Start: January 2, 2025
• Primary Completion (Estimated): October 2, 2027
• Study Completion (Estimated): December 2, 2028
• Last Updated: January 15, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)