Patients with resectable advanced stage HNSCC (T1–T4 N0-N2 M0) with intermediate risk (resection margins > 5 mm, no perineural invasion and no extracapsular evasion) for whom definite RT post surgery would be standard of care. MedDRA version: 21.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Nivolumab
Product Code: BMS-936558-01
Pharmaceutical Form: Solution for injection
Sponsors
Rheinische Friedrich-Wilhelms-Universität Bonn
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed squamous cell carcinoma of the head and neck region (oral cavity, pharynx, larynx), T1–T4 N0-N2 M0, with intermediate risk and curative intent for which post operative adjuvant radiation therapy would be standard of care. No presence of the following risk factors: extracapsular growth of the lymph nodes or positive margins; (in these cases an adjuvant post operation platinum based chemoradiation therapy is recommended). Close margins ( 5 mm; margins 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before study drug administration. 9. Have adequate organ function 10. Screening laboratory values must meet the following criteria (using CTCAE v4): • WBC ??2000/µL • Neutrophils ?1500/µL • Platelets ??100 x103/µL • Hemoglobin ? 9.0 g/dL • Serum creatinine ??1.5 x ULN or creatinine clearance (CrCl) > 40 mL/min • AST/ALT ??3 x ULN • Total Bilirubin ??1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Histologically confirmed recurrent or metastatic carcinoma or primary of the nasopharynx or salivary gland or non-squamous histologies (e.g. mucosal melanoma) are not allowed. 2. One of the following risk factors: extracapsular growth of the lymph nodes, or positive margins (post operative adjuvant platinum based chemoradiation therapy recommended). 3. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast. 4. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. 5. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 6. Prior treatment 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 co-stimulation or immune checkpoint pathways. 7. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results. 8. Patient is the recipient of an organ/bone marrow transplant 9. Positive test for Hepatitis B virus surface antigen (HB sAg) or active Hepatitis C (presence of HCV RNA in case of positive HCV antibody) or positive testing for HIV (HIV antibodies). 10. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). 11. History of allergy to study drug components. 12. History of severe hypersensitivity reaction to any monoclonal antibody. 13. Prisoners or subjects who are involuntarily incarcerated. 14. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness. 15. Current pregnancy or lactating females. 16. Females of childbearing potential, who are not using and not willing to use medically reliable methods of contraception for the entire study duration (such as oral, injectable or implantable contraceptives, or intrauterine contraceptive devices) unless they are surgically sterilized/hysterectomized or there are any other criteria sufficiently reliable by the investigator in individual cases. 17. The subject received an investigational drug within 30 days prior to inclusion into this study. 18. The subject is unwilling to provide informed consent or unwilling or unable to follow the procedures outlined in the protocol. 19. The subject is mentally or legally incapacitated.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To analyze response of intermediate risk HNSCC patients after surgery to treatment with nivolumab plus radiotherapy versus radiotherapy alone.;Secondary Objective: •To assess overall survival in response to experimental treatment versus standard treatment •To assess safety of nivolumab plus radiotherapy compared to radiotherapy alone •To assess quality of life of experimental treatment versus standard treatment Exploratory Objectives: •Identification of antigens recognized by the immune system under nivolumab plus radiotherapy compared to radiotherapy alone •To identify immunological biomarker for treatment response and prognosis ;Primary end point(s): Disease free survival measured from time of randomization to first signs of local recurrence, regional or distant metastasis, second primary or death, whichever comes first.;Timepoint(s) of evaluation of this end point: 36 month after randomization | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall survival, measured from time of randomisation to death of any cause • Adverse events (graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, V 4.0) • Quality of Life will be evaluated by standardized questionnaires QLQ-C30, EQ-5D and head and neck specific module QLQ-H&N35 Exploratory endpoints: • Immunological monitoring will consist of serum biomarkers, including but not limited to T cell response, characterization of immune cell subsets in peripheral blood, soluble PD-L1, soluble PD-L2, IL-2, inflammatory factors, rheumatoid factors. ;Timepoint(s) of evaluation of this end point: 36 month after randomization, over all survival will by assessed by long-term follow-up till death of any cause | — |
Countries
Germany
Contacts
Public ContactMarius Krauthausen
Studienzentrale Studienzentrum Bonn (SZB)
Outcome results
None listed