Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
Inclusion Criteria:
- Patients must have pathologically confirmed HPV-positive head and neck squamous cell
carcinoma of the oropharynx. Confirmed HPV-positive disease of other subsites are
uncommon but also eligible.
- HPV testing must be compliant with the following criteria:
- p16 IHC positivity is sufficient to enroll and initiate treatment (p16 IHC
interpretation to follow guidelines by Jordan and Lingen et al89).
- p16 IHC positivity is to be validated using an HPV PCR during the induction phase.
This is essential as HPV genotype influences treatment arm allocation, with
non-HPV16 HPV strains being considered high risk.
- Availability of ≥10 unstained 5 micron slides (to be provided to HTRC at the
University of Chicago). Patients who cannot fulfill this requirement will need to
undergo a new biopsy prior to enrollment on study.
- Patients must be at least 18 years of age.
- Patients with AJCC (7th edition, 2010) N2-N3 nodal disease or T3-T4 primary tumor.
- Measurable disease (either primary site and/or nodal disease) by RECIST 1.1
criteria.
- No previous radiation or chemotherapy for a head and neck cancer.
- No complete surgical resection for a head and neck cancer within 8 weeks of
enrollment (although lymph node biopsy including excision of an individual node with
presence of residual nodal disease, or surgical biopsy/excision of the tumor with
residual disease is acceptable).
- ECOG performance status 0-1 (Karnofsky greater than or equal to 80%).
- Normal Organ Function
- Leukocytes ≥3000/mm3,
- platelets ≥100,000/mm3,
- absolute neutrophil count ≥1,500,
- hemoglobin >9.0 gm/dL,
- AST and ALT <2.5 X ULN
- alkaline phosphatase <2.5 X ULN
- albumin >2.9 gm/dL, 29 Version Date: 12/28/2016
- total bilirubin ≤1.5 mg/dl,
- creatinine clearance >45 mL/min (or SCr <1.5 mg/dL), normal within 2 weeks prior to
start of treatment.
- The standard Cockcroft and Gault formula or the measured glomerular filtration rate
must be used to calculate CrCl for enrollment or dosing
- Patients must sign a study-specific informed consent form prior to study entry.
Patients should have the ability to understand and the willingness to sign a written
informed consent document.
- Age, Sex, and Reproductive Status:
1. Men and women, ages > 18.
2. Women of childbearing potential (WOCBP=premenopausal woman capable of becoming
pregnant) must have a negative serum or urine pregnancy test (minimum
sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the
start of study drug.
3. Women must not be breastfeeding.
4. WOCBP must agree to follow instructions for method(s) of contraception for the
duration of treatment with study drug(s) plus 5 half-lives of study drug(s)
plus 30 days (duration of ovulatory cycle) for a total of 23 weeks
post-treatment completion.
5. Men who are sexually active with WOCBP must agree to follow instructions for
method(s) of contraception for the duration of treatment with study drug(s)
plus 5 half-lives of study drug(s) plus 90 days (duration of sperm turnover)
for a total of 31 weeks post treatment completion.
6. Azoospermic males and WOCBP who are continuously not heterosexually active are
exempt from contraceptive requirements. However, they must still undergo
pregnancy testing as described in this section.
- Investigators shall counsel WOCBP and male subjects who are sexually active with
WOCBP on the importance of pregnancy prevention and the implications of an
unexpected pregnancy. Investigators shall advise WOCBP and male subjects who are
sexually active with WOCBP on the use of highly effective methods of contraception.
Highly effective methods of contraception have a failure rate of <1% when used
consistently and correctly.
- At a minimum subjects must agree to the use of one method of highly effective
contraception as listed below:
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION
- Hormonal methods of contraception including combined oral contraceptive pills,
vaginal ring, injectables, implants and intrauterine devices (IUDs) such as Mirena®
by WOCBP subject or male subject's WOCBP partner
- IUDs, such as ParaGard®
- Tubal ligation
- Vasectomy 30 Version Date: 12/28/2016
- Complete Abstinence*
- *Complete abstinence is defined as complete avoidance of heterosexual
intercourse and is an acceptable form of contraception for all study drugs.
Female subjects must continue to have pregnancy tests. Acceptable alternate
methods of highly effective contraception must be discussed in the event that
the subject chooses to forego complete abstinence.
Subjects are encouraged to use two methods of contraception, with one method being highly
effective and the other method being either highly effective or less effective as listed
below:
LESS EFFECTIVE METHODS OF CONTRACEPTION
- Diaphragm with spermicide
- Cervical cap with spermicide
- Vaginal sponge
- Male condoms and spermicide
- Male condom without spermicide
- Progestin only pills by WOCBP subject or male subject's WOCBP partner
- Female condom*
- *A male and female condom must not be used together
Exclusion Criteria:
- Unequivocal demonstration of distant metastases (M1 disease).
- Unidentifiable primary site.
- Intercurrent medical illnesses which would impair patient tolerance to therapy or
limit survival. Including but not limited to ongoing or active infection,
immunodeficiency, symptomatic congestive heart failure, pulmonary dysfunction,
cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance.
- Pregnant and nursing women are excluded because of the potential teratogenic effects
and potential unknown effects on nursing newborns (please see above paragraph under
inclusion criteria regarding WOCBP) 31 Version Date: 12/28/2016
- Prior surgical therapy other than incisional/excisional biopsy or organ-sparing
procedures such as debulking of airway-compromising tumors. Residual measurable
tumor is required for enrollment on study as outlined above
- Patients receiving other investigational agents.
- Peripheral neuropathy >grade 1
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy in
excess of physiologic dose or any other form of immunosuppressive therapy within 7
days prior to the first dose of trial treatment.
- Has a known history of active tuberculosis (Bacillus Tuberculosis infection)
- Has hypersensitivity to nivolumab or any other drug used in this protocol.
- Has had a prior systemic anti-cancer treatment within the last 8 weeks
- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of
the skin that has undergone potentially curative therapy or in situ cervical cancer
or any tumors that are not likely to influence live expectancy in the subsequent 3
years without active treatment (e.g. low grade prostate cancer in absence of
therapy).
- Has active autoimmune disease that has required systemic treatment in the past year
(i.e. with use of steroids or immunosuppressive drugs). Replacement therapy e.g.
levothyroxine, insulin, or physiologic corticosteroid doses for adrenal or pituitary
insufficiency, etc. are not considered a form of systemic treatment.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- Has a history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected). However, if eradicated patient is eligible.
- Has received a live vaccine within 28 days of planned start of study therapy. o
Note: Seasonal influenza vaccines for injection are generally inactivated flu
vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®)
are live attenuated vaccines, and are not allowed within 28 days prior to initiation
of treatment.