| Eligibility |
Inclusion Criteria:
- Patients must be 18 years of age and older.
- Pathologically confirmed SCCHN, not previously treated, with a plan to undergo surgery
- Patients who have stage III-IV disease without distant metastases (M0) of 1) oral
cavity, 2) larynx, 3) hypopharynx 4) oropharynx (human papillomavirus [HPV] neg) using
American Joint Committee on Cancer (AJCC) 8th edition
- Patients who have oropharyngeal cancer that HPV positive, stage II-III disease without
distant metastases (M0) using AJCC 8th edition
- All patients with oropharyngeal SCCHN must be tested for HPV (by p16 and/or HPV in
situ hybridization [ISH] or polymerase chain reaction [PCR])
- Patients must be evaluated by a head and neck surgeon and be deemed surgically
resectable at baseline
- Tumor sample must be available for HPV p16 and PD-L1 testing and if oropharyngeal,
must be tested for HPV p16
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- While blood cells 2000/ul or more
- Absolute neutrophil count 1500/ul or more
- Platelets 100,000/ul or more
- Hemoglobin 9 g/dl or more; (transfusion permitted)
- Bilirubin less than or equal to 1.5 x the upper limit of normal (except subjects with
Gilbert syndrome, who can have total bilirubin < 3 mg/dl)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal
to 3 x the upper limit of normal
- Glomerular filtration rate (GFR) greater than or equal to 40 ml/min using the
Cockcroft-Gault formula or serum creatinine less than or equal to 1.5 x upper limit of
normal (ULN)
- Women of reproductive potential should have a negative serum or urine pregnancy test
(minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin
[HCG]) within 21 days of study enrollment
- Women of reproductive potential must use highly effective contraception methods to
avoid pregnancy for 23 weeks after the last dose of study drugs; "women of
reproductive potential" is defined as any female who has experienced menarche and who
has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or
who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea
in a woman over 45 in the absence of other biological or physiological causes; in
addition, women under the age of 55 must have a documented serum follicle stimulating
hormone (FSH) level less than 40 mIU/mL
- Men of reproductive potential who are sexually active with women of reproductive
potential must use any contraceptive method with a failure rate of less than 1% per
year; men who are receiving the study medications will be instructed to adhere to
contraception for 31 weeks after the last dose of study drugs; men who are azoospermic
do not require contraception
- All subjects must be able to comprehend and sign a written informed consent document
Exclusion Criteria:
- Primary nasopharyngeal carcinoma
- Patients who have participated in a study with an investigational agent or device
within 2 weeks of initiation of treatment
- Any prior radiotherapy to the neck
- Any prior treatment for SCCHN
- Any prior therapy with anti-PD-1, anti-PD-L2, anti-CTLA-4 antibody, or any other
antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint
pathways
- Any history of a sever hypersensitivity reaction to any monoclonal antibody
- Any history of allergy to the study drug components
- Any concurrent malignancies- exceptions include- basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, superficial bladder cancer or in situ cervical
cancer that has undergone potentially curative therapy; patients with a history of
other prior malignancy must have been treated with curative intent and must have
remained disease-free for 3 years post-diagnosis
- Any diagnosis of immunodeficiency or current immunosuppressive therapy including
>10mg/day of prednisone within 14 days of enrollment is not permitted (excludes
emergency transient steroid use at discretion of the treating physician).
- Patients that have an active autoimmune disease requiring systemic treatment within
the past 3 months or a documented history of clinically severe autoimmune disease, or
a syndrome that requires systemic steroids (> 10 mg daily prednisone equivalents) or
immunosuppressive agents. Subjects with vitiligo, type I diabetes mellitus, or
resolved childhood asthma/atopy would be an exception to this rule. Inhaled or topical
steroids, and adrenal replacement steroid doses =10 mg daily prednisone equivalent,
are permitted in the absence of active autoimmune disease. Subjects with
hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be
excluded from the study.
- Patients with a known human immunodeficiency virus infection (HIV 1/2 antibodies) or
acquired immunodeficiency syndrome (HIV/AIDS), active hepatitis B (e.g., hepatitis B
surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV]
ribonucleic acid [RNA] [qualitative] is detected)
- Patients with evidence of non-infectious pneumonitis or history of interstitial lung
disease
- Patients who have received a live vaccine within 30 days prior initiation of the
systemic regimen
- Patients must not be receiving any other investigational agents
- Patients with uncontrolled intercurrent illnesses including, but not limited to an
active infection requiring systemic therapy or a known psychiatric or substance abuse
disorder(s) that would interfere with cooperation with the requirements of the trial
- Women must not be pregnant (as above) or breastfeeding
|
