| Eligibility |
Inclusion Criteria:
- Patients must be 18 years of age and older
- Pathologically confirmed squamous cell carcinoma of the head and neck (SCCHN), not
previously treated
- Stage III-IVB disease of 1) oral cavity, 2) HPV-negative (p16-) oropharynx, 3) larynx,
4) hypopharynx
- Oropharyngeal primaries that are HPV-mediated (p16+) must be stage II-III. Stage II
pateints must be either N2 or, if T3N0 or T3N1 they must also have at least 20 pack
year history of smoking
- Tumor sample must be available for HPV p16 and PD-L1 testing
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- White 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
- 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 24 hours of the start of study drugs
- 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 more 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
- Informed consent: all subjects must be able to comprehend and sign a written informed
consent document
Exclusion Criteria:
- Primary nasopharyngeal carcinoma
- Patients with brain metastases
- 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
- Patients with known contraindications to radiotherapy, including inherited syndromes
associated with hypersensitivity to ionizing radiation (e.g., Ataxia-Telangiectasia,
Nijmegen Breakage Syndrome)
- Any prior chemotherapy or radiation therapy for the current diagnosis
- 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
- 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 steroids </=10mg 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 evidence of interstitial lung disease or active, non-infectious
pneumonitis
- 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 who have received a live vaccine within 30 days prior to the radiation
therapy
- 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
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