The safety of nivolumab treatment in patients with oral cancer, and imaging using radioactive labelled anti-PD-L1 and radioactive glucose (sugar).

Phase 1

• Conditions: 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; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-002643-28-NL
• Lead Sponsor: Amsterdam UMC, location VUmc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-02-25
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 15

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

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified