Head and Neck Cancer Head and Neck Squamous Cell Carcinoma
Conditions
Interventions
After screening, eligible subjects will undergo a standard [18F]-FDG PET scan
and an experimental [18F]BMS-986192 PET scan. Patients will be treated with a
single dose of 480 mg of nivolumab followe
Sponsors
Vrije Universiteit Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Histologically confirmed diagnosis of locally advanced oral cancer (stage III/IV) which is planned for treatment with curative intent includiing surgical resection. - Must provide tissue from fresh tumor biopsy pretreatment and from the surgical resection material to determine actual PD-L1 status and perform immunomonitoring and DNA/RNA profiling. - Willing to allow up to two additional biopsies when baseline [18F]BMS-986192 PET /[18F]-FDG PET scans show heterogeneous and/or discrepant uptake. - ECOG performance scale 0-1 - Have adequate organ function (hematological, renal and hepatic) as demonstrated by screening laboratory test. - Women of childbearing potential must use appropriate method(s) of contraception during the study and for 23 week after the last dose of nivolumab - Men who are sexually active with women of childbearing potential must use any contraceptive method with a failure rate of less than 1% per year.
Exclusion criteria
Exclusion criteria: - Is currently participating in or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment or has not recovered (i.e., * Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. - Has a known current additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy or synchronous head and neck squamous cell carcinoma. - If subject received major surgery for any other reason, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. - Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of day -5. Inhaled or topical steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. - Has an active autoimmune disease requiring systemic steroid treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids. - Has evidence of interstitial lung disease or active, non-infectious pneumonitis. - Has an active infection requiring systemic therapy. - Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject*s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. - Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. - Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 23 weeks after the last dose of trial treatment. - Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways. -Has a known history of Human Immunodeficiency Virus infection with a detectable viral load. Patients with an undetectable load (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. To investigate heterogeneity in tumor uptake of [18F]BMS-986192 between patients and within tumor lesions of the same patient (primary tumor and TDLN/lymph node metastases) before treatment, in relation to changes in [18F]-FDG uptake before and on treatment. 2. To investigate the feasibility and safety of neoadjuvant nivolumab immunotherapy prior to surgery for locally advanced oral cancer. | — |
Secondary
| Measure | Time frame |
|---|---|
| 3. To investigate effects of nivolumab treatment on PD-L1 expression and availability for tracer binding in the patient and the relation to (changes in) [18F]-FDG uptake. 4. To investigate the relationship between [18F]BMS-986192 tumor uptake and tumor cell and tumor infiltrating lymphocyte (TIL) PD-1 and PD-L1 expression as well as other immune parameters. 5. To investigate changes in [18F]-FDG uptake during treatment. 6. To investigate the genomic profile of the tumor (neoantigens, mutational load, copy number changes and splice variants), in relation to [18F]BMS-986192 uptake, immune activation parameters and clinical response. 7. To investigate blood based analyses of the immuneprofile and plasma vesicle miRNAs on treatment and after treatment, in relation to immune activation parameters and clinical outcome. | — |
Countries
Netherlands
Outcome results
None listed