Stage III/IV resectable oral squamous cell carcinoma MedDRA version: 20.0 Level: LLT Classification code 10030961 Term: Oral cancer stage unspecified System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Opdivo
Product Name: Nivolumab
Product Code: BMS-936558
Pharmaceutical Form: Concentrate for solution for infusion
INN or Pr
Sponsors
Amsterdam UMC, location VUmc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria: 1. Have a histologically confirmed diagnosis of locally advanced oral cancer (stage III/IV) which is planned for treatment with curative intent including surgical resection. 2. Be willing and able to provide written informed consent/assent for the trial. 3. 18 years of age or older on day of signing informed consent. 4. Must agree to provide tissue from fresh tumor biopsy pretreatment and from the surgical resection material to determine the actual PD-L1 status and perform immunomonitoring/DNA/RNA profiling. 5. Willing to allow up to two additional biopsies when baseline [18F]BMS-986192 PET /[18F]-FDG PET scans show heterogeneous and/or discrepant uptake. 6. Have a performance status of 0-1 on the ECOG Performance Scale. 7. Demonstrate adequate organ function as defined in Table 1. All screening labs should be performed within 2 weeks before any study imaging procedures are performed. Table 1 Adequate Organ Function Laboratory Values System Laboratory Value Hematological White blood cell count (WBC) =2,000 /mcL Absolute neutrophil count (ANC) =1,500 /mcL Platelets =100,000 / mcL Hemoglobin =9 g/dL or =5.6 mmol/L Renal Serum creatinine OR =1.5 X upper limit of normal (ULN) measured or calculated creatinine clearance =30 mL/min for subject with creatinine levels > 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl) Hepatic Serum total bilirubin Total Bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) AST (SGOT) and ALT (SGPT) = 3 X ULN 8. Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception during the study and for 23 weeks after the last dose of nivolumab. Women who are not of childbearing potential (i.e. who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception. 9. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception during the study and for 31 weeks after the last dose of nivolumab. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Num
Exclusion criteria
Exclusion criteria: A subject who meets any of the following criteria will be excluded from participation in this study: 1. 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. 2. Has had another known invasive malignancy within the previous 5 years and/or has had surgery, chemotherapy, targeted small molecule therapy or radiation therapy within 5 years for a known malignancy prior to study day 0. 3. 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. 4. 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. 5. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of day 0. Inhaled or topical steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. 6. 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. 7. Has evidence of interstitial lung disease or active, non-infectious pneumonitis. 8. Has an active infection requiring systemic therapy. 9. 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. 10. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 11. 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. 12. 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. 13. Has a known history of Human Immunodeficiency Virus (HIV) infection (HIV 1/2 antibodies). 14. Has known active Hepatitis B or C.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1. PET imaging T0 = baseline T2 = two weeks after nivolumab treatment 2. (Serious) adverse events Throughout entire study ; Main Objective: 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 Objective: 1. 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. 2. 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. 3. To investigate changes in [18F]-FDG uptake during treatment. 4. 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. 5. 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. ; Primary end point(s): 1. PET Imaging [18F]BMS-986192 and [18F]-FDG SUVmax, SUVmean, SUVpeak will be measured in all tumor lesions and (enlarged) lymph nodes using manually drawn volumes of interest (VOI) before and on treatment. For [18F]BMS-986192 manually drawn VOIs will also be calculated for liver, kidneys, | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Heterogeneity analysis Interpatient, intrapatient and intratumor SUV heterogeneity. 2. Correlation between PET scans, and between imaging and response The correlation between SUV for [18F]BMS-986192 and [18F]-FDG baseline and on treatment and early response evaluation with [18F]-FDG. 3. Correlation between PET data and Blood/Tissue markers The correlation between continuous values as SUV and the categorical variables tissue PD-1 and PD-L1 IHC will be assessed for each tumor lesion. Correlation with immunomonitoring analysis in tumor tissue/lymph nodes and blood, plasma vesicle miRNAs from blood, as well as DNA/RNA profiling in tumor tissue at baseline and at surgery will be assessed. ; Timepoint(s) of evaluation of this end point: 1. Heterogeneity analysis T0 = baseline T2 = two weeks after nivolumab treatment T3 = after surgery 2. Correlation between PET scans, and between imaging and response T0 = baseline T2 = two weeks after nivolumab treatment 3. Correlation between PET data and Blood/Tissue markers T0 = baseline T2 = two weeks after nivolumab treatment T3 = after surgery | — |
Countries
Netherlands
Contacts
Public ContactDr. C.W. Menke-van Houven van Oordt
Amsterdam UMC, locatie VUmc
Outcome results
None listed