Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma
Condition: Cancer of Head and Neck; Head and Neck Cancer; Neoplasms, Head and Neck; Carcinoma, Squamous Cell of Head and Neck; Squamous Cell Carcinoma of the Head and Neck; Squamous Cell Carcinoma, Head and Neck
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck
Intervention: MK-3475 (neoadjuvant); Surgery; Intensity modulated radiation therapy; Image-guided radiation therapy; Cisplatin; MK-3475 (adjuvant); Peripheral blood
Intervention description: Standard of care; Recommended, standard of care; Recommended, standard of care; Standard of care; -Baseline, time of surgery (between day 14-24 inclusive), 3 months post surgery, 6 months post surgery, 9 months post surgery, 12 months post surgery
Intervention MeSH terms: Cisplatin; Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 67.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The goal of this trial is to test the ability of MK-3475 (pembrolizumab) to improve
      locoregional recurrence and distant metastatic rates in high-risk patients with locally
      advanced head and neck squamous cell carcinomas (HNSCCs) that are treated with current
      standard of care surgical approaches.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed stage III or IV HNSCC oral cavity,
             hypopharynx, oropharynx, larynx (excluding p16 or HPV-positive oropharynx primaries
             and sinonasal primaries).

          -  Measurable disease defined as lesions that can be accurately measured in at least one
             dimension (longest diameter to be recorded) as >10 mm with CT scan, as >20 mm by chest
             x-ray, or >10 mm with calipers by clinical exam by RECIST 1.1.

          -  At least 18 years of age.

          -  ECOG performance status ≤ 1

          -  Normal bone marrow and organ function as defined below:

               -  Absolute neutrophil count ≥ 1,500/mcl

               -  Platelets ≥ 100,000/mcl

               -  Hemoglobin ≥ 9 g/dL

               -  Total bilirubin ≤ 1.5 x IULN OR Direct bilirubin ≤ IULN for patients with total
                  bilirubin > 1.5 x IULN

               -  AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (or ≤ 5 x IULN for patients with liver
                  metastases)

               -  Serum creatinine ≤ 1.5 x IULN OR Creatinine clearance by Cockcroft-Gault ≥ 30
                  mL/min/1.73 m2 for patients with creatinine levels > 1.5 x IULN

               -  INR ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR
                  or PTT is within therapeutic range of intended use of anticoagulants

               -  aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as
                  INR or PTT is within therapeutic range of intended use of anticoagulants

          -  Sexually active women of childbearing potential and men must agree to use 2 methods of
             contraception (hormonal or barrier method of birth control, abstinence) prior to study
             entry, for the duration of study participation, and for 120 days after last dose of
             MK-3475. Should a woman become pregnant or suspect she is pregnant while participating
             in this study, she must inform her treating physician immediately.

          -  Ability to understand and willingness to sign an IRB approved written informed consent
             document (or that of legally authorized representative, if applicable).

        Exclusion Criteria:

          -  Prior treatment for head and neck cancer.

          -  Patients with HPV-positive or p16-positive oropharyngeal SCCA.

          -  Patients with sinonasal SCCAs

          -  Patients with metastatic SCCA neck disease with an unknown primary tumor site

          -  Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
             anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
             ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
             or checkpoint pathways).

          -  Received a live vaccine within 30 days prior to the first dose of MK-3475. Examples of
             live vaccines include, but are not limited to, the following: measles, mumps, rubella,
             varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG),
             and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed
             virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist)
             are live attenuated viruses and are not allowed.

          -  A history of other malignancy ≤ 3 years previous with the exception of previous head
             and neck cancer treated only by surgery, basal cell or squamous cell carcinoma of the
             skin which were treated with local resection only, or carcinoma in situ of the cervix.

        Note: patients with synchronous head and neck cancer primaries are an exception to this
        criterion and may qualify for the study.

          -  Has a diagnosis of immunodeficiency or is receiving 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 MK-3475.

          -  Currently receiving any other investigational agents or has participated in a study of
             an investigational agent or using an investigational device within 4 weeks of the
             first dose of MK-3475.

          -  A history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to MK-3475 or other agents used in the study.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection requiring systemic therapy, symptomatic congestive heart failure, unstable
             angina pectoris, cardiac arrhythmia, immunosuppression, autoimmune conditions,
             underlying pulmonary disease, or psychiatric illness/social situations that would
             limit compliance with study requirements.

          -  Has an active autoimmune disease that has required systemic treatment in the past 2
             years (i.e. with use of disease modifying agents, corticosteroids, or
             immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
             physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
             etc.) is not considered a form of systemic treatment.

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis.

          -  Pregnant and/or breastfeeding. Patient must have a negative serum or urine pregnancy
             test within 72 hours of study entry.

          -  Known history of active TB (bacillus tuberculosis).

          -  Known history of hepatitis B (defined as hepatitis B survace antigen [HBsAg] reactive)
             or known active hepatitis C (defined as HCV RNA [qualitative] is detected) infection.
             Note: know testing for hepatitis B and hepatitis C is required unless mandated by
             local health authority.

          -  Known history of HIV (HIV 1/2 antibodies).