neoplasms squamous cell carcinoma head and neck head and neck cancer squamous cell carcinoma
Conditions
Interventions
Concurrent Radiation therapy (i.e. 5 times a week, 7 weeks, total dose 70 Gy)
with cetuximab (loading dose 400 mg/m2 i.v. day -7, 250 mg/m2 i.v weekly wk
1-6) and Avelumab10 mg/kg i.v. at day -7, 7,
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
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
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Toxicity measured according to CTC 4.03 | — |
Secondary
| Measure | Time frame |
|---|---|
| Response Rates (i.e. CR, PR, SD, PD) Differences in tumor microenvironment in biopsies of the primary tumor site obtained prior and at day +14 of treatment. | — |
Countries
Netherlands
Outcome results
None listed