| Eligibility |
Inclusion Criteria:
- Participants must have histologically or cytologically confirmed locoregionally
recurrent squamous cell carcinoma of the head and neck (including primary sites, such
as oral cavity, oropharynx, larynx or hypopharynx carcinoma).
- Participants must be a candidate for salvage surgery.
- Participants must have documented time of = 6 months from completion of prior curative
intent treatment for HNSCC (surgery and/or radiation therapy with/without platinum
chemotherapy or cetuximab targeted therapy) to diagnosis of local or locoregional
recurrence.
- Participants must be willing to undergo a mandatory pre-treatment biopsy and willing
to provide blood and tissue from the pre-treatment biopsy and at the time of surgery.
Exceptions may be made after discussion with sponsor if it is not medically feasible
to obtain a pre-treatment biopsy. Archival tissue may be collected in this situation.
Participants will be offered the opportunity to volunteer for optional biopsies at the
time of recurrence of disease.
- Participants may have any smoking history (no restrictions)
- Participants may have any Human Papilloma Virus (HPV) status of the tumor. Patients
with oropharyngeal cancer are required to undergo HPV testing with p16
immunohistochemistry and/or confirmatory HPV PCR or ISH testing
- Age =18 years
- ECOG performance status 0 or 1 (Karnofsky =70%, see Appendix A)
- Participants must have adequate organ and marrow function as defined below:
- leukocytes =3,000/mcL
- absolute neutrophil count =1,500/mcL
- platelets =100,000/mcL
- total bilirubin = institutional upper limit of normal (ULN)
- AST(SGOT)/ALT(SGPT) =3 × institutional ULN
- creatinine = institutional ULN OR
- glomerular filtration rate (GFR) =50 mL/min/1.73 m2 unless data exists supporting
safe use at lower kidney function values, no lower than 30 mL/min/1.73 m2.
- Participants with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, participants should be class 2B or better.
- Because pembrolizumab and chemotherapy can be teratogenic, women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier method
of birth control; abstinence) prior to study entry and for the duration of study
participation. Should a woman become pregnant or suspect she is pregnant while she or
her partner is participating in this study, she should inform her treating physician
immediately.
- Male participants: A male participant must agree to use a contraception as detailed in
Appendix B of this protocol during the treatment period and for at least 180 days
after the last dose of study treatment and refrain from donating sperm during this
period.
- Female participants: A female participant is eligible to participate if she is not
pregnant (see Appendix B), not breastfeeding, and at least one of the following
conditions applies:
- a. Not a woman of childbearing potential (WOCBP) as defined in Appendix B OR
- b. A WOCBP who agrees to follow the contraceptive guidance in Appendix B during
the treatment period and for at least 180 days after the last dose of study
treatment.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Sinonasal, nasopharyngeal or cutaneous primary site of squamous cell carcinoma of the
head and neck
- Has known distant metastatic disease. Those with known brain metastases should be
excluded from this clinical trial, because of the poor prognosis and because they
often develop progressive neurologic dysfunction that would confound the evaluation of
neurologic and other adverse events. However, baseline brain imaging is not required
prior to enrollment in the study if patients are asymptomatic
- Has had chemotherapy or radiotherapy for HNSCC in curative intent setting within 6
months prior to entering the study.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,
OX 40, CD137).
- Has received a live vaccine or live-attenuated vaccine within 30 days prior to the
first dose of study drug. Administration of killed vaccines is allowed
- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
study intervention.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug
- Has a known additional malignancy that is progressing or has required active treatment
within the past 2 years. Participants with basal cell carcinoma of the skin, squamous
cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer
in situ) that have undergone potentially curative therapy are not excluded
- Has a history of allergic reactions to agents used in study
- Has active autoimmune disease that has required systemic treatment in past 2 years
(ie, with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a form
of systemic treatment and is allowed
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is
required unless mandated by local health authority
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required
unless mandated by local health authority.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the participant's
participation for the full duration of the study, or is not in the best interest of
the participant to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
- Has not recovered from adverse events due to prior anti-cancer therapy (i.e., have
residual toxicities > Grade 2) with the exception of alopecia
- Has had an allogeneic tissue/solid organ transplant
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to study
registration (see Appendix B). If the urine test is positive or cannot be confirmed as
negative, a serum pregnancy test will be required. Pregnant women are excluded from
this study because pembrolizumab and chemotherapy agents have the potential for
teratogenic or abortifacient effects. Because there is an unknown but potential risk
for adverse events in nursing infants secondary to treatment of the mother with
pembrolizumab and chemotherapy, breastfeeding should be discontinued if the mother is
treated on this protocol.
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