Atezolizumab Before Surgery for the Treatment of Regionally Metastatic Head and Neck Squamous Cell Cancer With an Unknown or Historic Primary Site
Condition: Locally Advanced Cutaneous Squamous Cell Carcinoma of the Head and Neck; Resectable Cutaneous Squamous Cell Carcinoma of the Head and Neck; Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: Atezolizumab; Radiation Therapy; Therapeutic Conventional Surgery
Intervention description: Given IV; Undergo radiation therapy; Undergo surgery
Intervention MeSH terms: Atezolizumab; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial tests whether atezolizumab works to shrink tumors before surgery in
      patients with head and neck squamous cell cancer with an unknown or historic primary site
      that has spread to other places in the lymph nodes (regionally metastatic). Immunotherapy
      with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack
      the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving
      atezolizumab before surgery may reduce the size of the tumor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants with biopsy proven, surgically resectable head and neck cutaneous
             squamous cell carcinoma regionally metastatic to lymph nodes in the head and/or neck
             with a historical or unknown (but not concurrent) primary site

          -  Patients must be >= 18 years

          -  Patients with resectable regionally metastatic HNCSCC from an unknown or historical
             primary and no evidence of distant metastatic disease

          -  Full decision-making capacity and consent provided and documented

          -  Radiographically measurable disease per immune Response Evaluation Criteria in Solid
             Tumors (iRECIST)

          -  Surgically resectable disease per standard of care (SoC)

          -  For Women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraceptive methods as defined below: * Women must
             remain abstinent or use contraceptive methods with a failure rate of < 1% per year
             during the treatment period and for 5 months after the final dose of atezolizumab * A
             woman is considered to be of childbearing potential if she is postmenarchal, has not
             reached a postmenopausal state (>= 12 continuous months of amenorrhea with no
             identified cause other than menopause), and has not undergone surgical sterilization
             (removal of ovaries and/or uterus). The definition of childbearing potential may be
             adapted for alignment with local guidelines or requirements * Examples of
             contraceptive methods with a failure rate of < 1% per year include bilateral tubal
             ligation, male sterilization, hormonal contraceptives that inhibit ovulation,
             hormone-releasing intrauterine devices, and copper intrauterine devices * The
             reliability of sexual abstinence should be evaluated in relation to the duration of
             the clinical trial and the preferred and usual lifestyle of the patient. Periodic
             abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and
             withdrawal are not adequate methods of contraception

          -  Men: abstinent or using effective contraception method

          -  Tumor tissue sample adequate for PD-L1 and biomarker studies

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Availability of a representative tumor specimen for exploratory biomarker research

          -  Life expectancy >= 2 years

          -  Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (1500/uL) without granulocyte
             colony-stimulating factor support (within 14 days prior to initiation of study
             treatment)

          -  Lymphocyte count >= 0.5 x 10^9/L (500/uL) (within 14 days prior to initiation of study
             treatment)

          -  Platelet count >= 50 x 10^9/L (50,000/uL) without transfusion (within 14 days prior to
             initiation of study treatment)

          -  Hemoglobin >= 80 g/L (8 g/dL) (within 14 days prior to initiation of study treatment)
             * Patients may be transfused to meet this criterion

          -  Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline
             phosphatase (ALP) =< 2.5 x upper limit of normal (ULN) (within 14 days prior to
             initiation of study treatment)

          -  Serum bilirubin =< 1.5 x ULN (within 14 days prior to initiation of study treatment)
             with the following exception: * Patients with known Gilbert disease: serum bilirubin
             =< 3 x ULN

          -  Serum creatinine =< 1.5 x ULN or creatinine clearance >= 60 mL/min (calculated using
             the Cockcroft-Gault formula (within 14 days prior to initiation of study treatment)

          -  Serum albumin >= 25 g/L (2.5 g/dL) (within 14 days prior to initiation of study
             treatment)

          -  For patients not receiving therapeutic anticoagulation: international normalized ratio
             (INR) or activated partial thromboplastin time (aPTT) =< 1.5 x ULN

          -  For patients receiving therapeutic anticoagulation: stable anticoagulant regimen

          -  Negative human immunodeficiency virus (HIV) test at screening with the following
             exception: patients with a positive HIV test at screening are eligible provided they
             are stable on anti-retroviral therapy, have a CD4 count >= 200, and have an
             undetectable viral load

          -  Negative hepatitis B surface antigen (HBsAg) test at screening

          -  Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total
             HBcAb test followed by a negative hepatitis B virus (HBV) deoxyribonucleic acid (DNA)
             test at screening

          -  The HBV DNA test will be performed only for patients who have a negative HBsAg test
             and a positive total HBcAb test

        Exclusion Criteria:

          -  Distant metastatic disease

          -  Unresectable disease: As defined by: common or internal carotid artery encasement or
             involvement of the skull base involvement or pre-vertebral fascia

          -  Uncontrolled tumor-related pain

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures (once monthly or more frequently) * Patients with indwelling
             catheters (e.g., PleurX) are allowed

          -  Uncontrolled (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum
             calcium > ULN) or symptomatic hypercalcemia

          -  Active or history of autoimmune disease or immune deficiency, including, but not
             limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid
             antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome,
             or multiple sclerosis, with the following exceptions: * Patients with a history of
             autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible
             for the study * Patients with controlled type 1 diabetes mellitus who are on an
             insulin regimen are eligible for the study * Patients with eczema, psoriasis, lichen
             simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients
             with psoriatic arthritis are excluded) are eligible for the study provided all of
             following conditions are met: ** Rash must cover < 10% of body surface area ** Disease
             is well controlled at baseline and requires only low-potency topical corticosteroids
             ** No occurrence of acute exacerbations of the underlying condition requiring psoralen
             plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral
             calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12
             months * Any history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g.,
             bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or
             evidence of active pneumonitis on screening chest computed tomography (CT) scan.
             History of radiation pneumonitis in the radiation field (fibrosis) is permitted

          -  Known active tuberculosis

          -  Significant cardiovascular disease (such as New York Heart Association class II or
             greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3
             months prior to initiation of study treatment, unstable arrhythmia, or unstable angina

          -  Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation
             of study treatment, or anticipation of need for a major surgical procedure during the
             study

          -  History of malignancy within 2 years prior to screening, with the exception of
             malignancies with a negligible risk of metastasis or death (e.g., 5-year overall
             survival [OS] rate > 90%), such as adequately treated carcinoma in situ of the cervix,
             non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or
             stage I uterine cancer

          -  Severe infection within 4 weeks prior to initiation of study treatment, including, but
             not limited to, hospitalization for complications of infection, bacteremia, or severe
             pneumonia. Severe infection is defined as that requiring inpatient treatment of
             hospitalization

          -  Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
             of study treatment * Patients receiving prophylactic antibiotics (e.g., to prevent a
             urinary tract infection or chronic obstructive pulmonary disease exacerbation) are
             eligible for the study

          -  Prior allogeneic stem cell or solid organ transplantation

          -  Any other disease, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding that contraindicates the use of an investigational drug, may affect
             the interpretation of the results, or may render the patient at high risk from
             treatment complications

          -  Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study
             treatment, or anticipation of need for such a vaccine during atezolizumab treatment or
             within 6 months after the final dose of atezolizumab

          -  Current treatment with anti-viral therapy for HBV. Patient on suppressive therapy
             should excluded

          -  Treatment with investigational therapy within 28 days prior to initiation of study
             treatment

          -  Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including
             anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies

          -  Treatment with systemic immunostimulatory agents (including, but not limited to,
             interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug
             (whichever is longer) prior to initiation of study treatment

          -  Treatment with systemic immunosuppressive medication (including, but not limited to,
             corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
             anti-TNF-alpha agents) within 2 weeks prior to initiation of study treatment, or
             anticipation of need for systemic immunosuppressive medication during study treatment,
             with the following exceptions: * Patients who received acute, low-dose (defined as <
             200 mg / day hydrocortisone or equivalent) corticosteroid treatment (e.g., 48 hours of
             corticosteroids for a contrast allergy) are eligible for the study after principal
             investigator confirmation has been obtained * Patients who received mineralocorticoids
             (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease
             (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal
             insufficiency are eligible for the study

          -  History of severe allergic anaphylactic reactions to chimeric or humanized antibodies
             or fusion proteins

          -  Known hypersensitivity to Chinese hamster ovary cell products or to any component of
             the atezolizumab formulation

          -  Concurrent identifiable primary cutaneous head and neck squamous cell carcinoma tumor

          -  Pregnant or breastfeeding, or intention of becoming pregnant during study treatment or
             within 5 months after the final dose of study treatment