Bioimmunoradiotherapy (BIR) with concurrent Avelumab, Cetuximab and Radiotherapy as first line treatment in patients with locally advanced squamous cell carcinoma of the head and neck. A feasibility study in patients unfit for cisplati

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 10

Inclusion Criteria

1. Be willing and able to provide written informed consent for the trial.
2. Be *18 years of age on day of signing informed consent.
3. WHO Performance Status 0-2
4. Histologically confirmed Locally Advanced (i.e. stage III or IV) head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx.
5. Unfit for concurrent chemoradiation with cisplatin, e.g. GFR < 60 ml/min, cardiovascular co-morbidity, hearing loss or polyneuropathy or written confirmed unwillingness for treatment with chemotherapy
6. Willingness to provide tissue for tumor microenvironment analysis from archival tumor material or newly obtained core or excisional biopsy and willingness to provide a core or excisional biopsy at day 14 (±2 days) after start of treatment.
7. At least one measurable lesion as defined by RECIST 1.1.
8. Patients who are willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
9. Adequate bone marrow, renal and liver function.
10. Serum pregnancy test (for females of childbearing potential) negative at screening.
11. Highly effective contraception for both male and female subjects if the risk of conception exists.

Exclusion Criteria

1. The following prior therapies are excluded:
* Prior systemic therapy, radiotherapy or surgery directed at locally advanced SCCHN.
* Prior immunotherapy with IL-2, IFN-*, or anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
2. A diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
3. Current or prior use of immunosuppressive medication within 7 days prior to
randomization, (see protocol for exceptions)
4. Known severe hypersensitivity reactions to monoclonal antibodies (Grade *3), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partially controlled asthma).
5. Known prior or suspected hypersensitivity to study drugs or any component in their formulations.
6. Diagnosis of any other malignancy within 5 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason 6 or below) prostate cancer on surveillance with no plans for treatment intervention (eg, surgery, radiation, or castration).
7. Significant acute or chronic infections.
8. Prior organ transplantation, including allogeneic stem cell transplantation
9. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent, but
a. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
b. Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses * 10 mg or 10 mg equivalent prednisone per day
c. Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable
10. Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v 4.03; however, alopecia and sensory neuropathy Grade * 2 is acceptable
11. Pregnancy or lactation
12. Known alcohol or drug abuse
13. All other significant diseases, which, in the opinion of the Investigator, might impair the subject*s tolerance of trial treatment
14. Any psychiatric condition that would prohibit the understanding or rendering of informed consent
15. Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated influenza vaccines).
16. Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis or symptomatic pulmonary embolism.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Toxicity measured according to CTC 4.03</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Response Rates (i.e. CR, PR, SD, PD)<br /><br>Differences in tumor microenvironment in biopsies of the primary tumor site<br /><br>obtained prior and at day +14 of treatment.</p><br>