| Eligibility |
Inclusion Criteria:
- Written informed consent obtained to participate in the study and HIPAA authorization
for release of personal health information. Consent for the use of any residual
material from biopsy (archival tissue) and serial blood draws will be required for
enrollment.
- Age = 18 years of age on day of signing informed consent
- ECOG Performance Status of 0 or 1 (See Appendix 12.4: ECOG Performance Status)
- Histologically confirmed squamous cell carcinoma of the head and neck, including the
following subtypes: oral cavity, oropharynx, hypopharynx, larynx
- Must have undergone gross total resection of the primary tumor with curative intent
within the past 8 weeks with surgical pathology demonstrating = 1 of the following
criteria for "intermediate" risk of recurrence:
- perineural invasion
- lymphovascular invasion
- single lymph node > 3 cm or at least 2 nodes without evidence of extracapsular
extension
- close margins defined as < 5 mm but not frankly positive (in the case of
ambiguous, controversial, or superseded margins, final clinical assessment
regarding margin status will prevail)
- pathologically confirmed T3 or T4 primary tumor
- No prior therapy to primary tumor prior to surgical resection (no induction therapy or
recurrent disease).
- Demonstrated adequate organ function as defined in the protocol
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test
within 7 days prior to treatment. NOTE: Females are considered of child bearing
potential unless they are surgically sterile (have undergone a hysterectomy, bilateral
tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at
least 12 consecutive months. Documentation of postmenopausal status must be provided.
- WOCBP must be willing to abstain from heterosexual activity or to use at least 1
highly effective method of contraception from the time of informed consent until 90
days after durvalumab monotherapy treatment is discontinued (whichever is longer). See
section 5.6 of the protocol for additional details on contraception requirements for
WOCBP and male participants in this trial.
- Male patients with female partners must have had a prior vasectomy or agree to use an
adequate method of contraception (i.e., double barrier method: condom plus spermicidal
agent) starting with the first dose of study therapy through 90 days after durvalumab
monotherapy is discontinued.
- Subjects must be willing and able to comply with study procedures based on the
judgment of the investigator or protocol designee.
Exclusion Criteria:
Subjects meeting any of the following exclusion criteria will not be able to participate in
this study:
- Is currently participating in or has participated in a study of an investigational
agent or an investigational device within 4 weeks of the first dose of treatment.
- Concurrent enrollment in another clinical study, unless it is an observational
(non-interventional) clinical study or during the follow-up period of an
interventional study.
- Has evidence of metastatic disease at time of diagnosis
- Is receiving concurrent chemotherapy, investigational drug, biologic, or hormonal
therapy for cancer treatment. Concurrent use of hormonal therapy for
non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
- Treatment with any investigational drug within 28 days or 5 half-lives of Day 1 of
treatment on this study, whichever is shortest.
- Has not received any antibiotics <7 days prior to 1st dose of durvalumab. If the
patient receives either IV antibiotics or >5 day treatment course (oral or IV), then
the 1st durvalumab dose should not be given until 14 days of last antibiotic dose.
During eligibility screening, subjects who receive any antibiotics within 30 days
prior to the proposed initial infusion of durvalumab should be flagged and reviewed by
the site's Principle Investigator to determine if the subject is a good candidate to
receive durvalumab.
- Known allergy or hypersensitivity to durvalumab or any of the study drug excipients.
- Prior randomization or treatment in a previous durvalumab clinical study regardless of
treatment arm assignment.
- Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
- Has received systemic steroid therapy or any other form of immunosuppressive therapy
within 7 days prior to the first dose of trial treatment.
- Active infection requiring systemic therapy including tuberculosis (clinical
evaluation that includes clinical history, physical examination and radiographic
findings, and TB testing in line with local practice), hepatitis B (known positive HBV
surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus
(positive HIV 1/2 antibodies).
- Patients with a past or resolved HBV infection (defined as the presence of
hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible.
- Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase
chain reaction is negative for HCV RNA.
- Has a known contraindication to radiation therapy, including inherited syndromes
associated with hypersensitivity to ionizing radiation such as Ataxia-Telangiectasia
and Nijmegen Breakage Syndrome
- Has a history of uncontrolled liver disease (including but not limited to cirrhosis).
- Subjects with baseline weight = 40kg (88 lbs).
- Female patients who are pregnant or breastfeeding (NOTE: breast milk cannot be stored
for future use while the mother is being treated on study) or male or female patients
of reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab monotherapy.
- History of another primary malignancy except for.
- Malignancy treated with curative intent and with no known active disease =5 years
before the first dose of IP and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease
- Adequately treated carcinoma in situ without evidence of disease
- History of leptomeningeal carcinomatosis.
- Has an active autoimmune disease (or inflammatory disorders) requiring systemic
treatment within the past 3 months or a documented history of clinically severe
autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive
agents. Subjects with inflammatory disorders (including inflammatory bowel disease
[e.g., colitis or Crohn's disease], diverticulitis [with the exception of
diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener
syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis,
hypophysitis, uveitis, etc]).
The following are exceptions to this criterion:
- Subjects with vitiligo or alopecia or resolved childhood asthma/atopy
- Subjects who require intermittent use of bronchodilators or local steroid injections
would not be excluded from the study.
- Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone
replacement or with Sjorgen's syndrome will not be excluded from the study
- Any chronic skin condition that does not require systemic therapy
- Subjects without active HNSCC disease in the last 5 years may be included but only
after consultation with the study physician
- Subjects with celiac disease controlled by diet alone
- Has a history of non-infectious pneumonitis that required steroids or evidence of
interstitial lung disease or current active, non-infectious pneumonitis.
- Major surgical procedure (as defined by the Investigator) within 21 days prior to
the first dose of investigational product (IP). Note: Local surgery of isolated
lesions for palliative intent is acceptable.
- Uncontrolled intercurrent illness, including but not limited to, ongoing or
active infection, symptomatic congestive heart failure, uncontrolled
hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung
disease, serious chronic gastrointestinal conditions associated with diarrhea, or
psychiatric illness/social situations that would limit compliance with study
requirement, substantially increase risk of incurring AEs or compromise the
ability of the patient to give written informed consent.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of
study drug. Note: Patients, if enrolled, should not receive live vaccine whilst
receiving study treatment and up to 30 days after the last dose of study
treatment.
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