Clinical Trials /

Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma

NCT02296684

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Immunotherapy</span> With <span class="go-doc-concept go-doc-intervention">MK-3475</span> in Surgically Resectable Head and Neck Squamous Cell Carcinoma

Title

  • Brief Title: Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma
  • Official Title: Immunotherapy With MK-3475 in Locoregionally Advanced, Surgically Resectable Head and Neck Squamous Cell Carcinoma
  • Clinical Trial IDs

    NCT ID: NCT02296684

    ORG ID: 201412118

    Trial Conditions

    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

    Trial Interventions

    Drug Synonyms Arms
    Cisplatin cis-DDP, cis-Platinum II, cis-Diamminedichloroplatinum, DDP Neoadjuvant MK-3475 and Adjuvant MK-3475

    Trial Purpose

    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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Neoadjuvant MK-3475 and Adjuvant MK-3475 Experimental MK-3475 will be given intravenously over the course of 30 minutes once approximately 2-3 weeks prior to standard of care surgery. Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) optional image-guided radiation therapy risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based on 's surgical pathology from standard of care surgery shows high risk features (positive margins or extracapsular extension). These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less. Cisplatin

    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 60
    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.

    - 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 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, 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 known history of or any evidence of active, non-infectious 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 active hepatitis B (e.g. HBsAg reactsive) or hepatitis C (e.g. HCV RNA
    [qualitative] is detected).

    - Known history of HIV (HIV 1/2 antibodies).

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Locoregional recurrence rates

    Distant failure rate

    Secondary Outcome Measures

    Occurrence of adverse events

    Surgical complications and/or delays

    Trial Keywords