Safety and tolerability of neoadjuvant nivolumab for locally advanced resectable oral cancer, combined with [18F]BMS-986192 / [18F]-FDG PET imaging and immunomonitoring for response prediction.
- Conditions
- Head and Neck CancerHead and Neck Squamous Cell Carcinoma10027655
- Registration Number
- NL-OMON50077
- Lead Sponsor
- Vrije Universiteit Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
- 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.
- 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 (<50 copies/ml)
receiving adequate anti-retroviral therapy, are allowed to participate.
- Has known active Hepatitis B or C.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>1. To investigate heterogeneity in tumor uptake of [18F]BMS-986192 between<br /><br>patients and within tumor lesions of the same patient (primary tumor and<br /><br>TDLN/lymph node metastases) before treatment, in relation to changes in<br /><br>[18F]-FDG uptake before and on treatment.<br /><br>2. To investigate the feasibility and safety of neoadjuvant nivolumab<br /><br>immunotherapy prior to surgery for locally advanced oral cancer. </p><br>
- Secondary Outcome Measures
Name Time Method <p>3. To investigate effects of nivolumab treatment on PD-L1 expression and<br /><br>availability for tracer binding in the patient and the relation to (changes in)<br /><br>[18F]-FDG uptake.<br /><br>4. To investigate the relationship between [18F]BMS-986192 tumor uptake and<br /><br>tumor cell and tumor infiltrating lymphocyte (TIL) PD-1 and PD-L1 expression as<br /><br>well as other immune parameters.<br /><br>5. To investigate changes in [18F]-FDG uptake during treatment.<br /><br>6. To investigate the genomic profile of the tumor (neoantigens, mutational<br /><br>load, copy number changes and splice variants), in relation to [18F]BMS-986192<br /><br>uptake, immune activation parameters and clinical response.<br /><br>7. To investigate blood based analyses of the immuneprofile and plasma vesicle<br /><br>miRNAs on treatment and after treatment, in relation to immune activation<br /><br>parameters and clinical outcome.</p><br>