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

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

  • ORG STUDY ID: 201412118
  • NCT ID: NCT02296684

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

Interventions

DrugSynonymsArms
MK-3475 (neoadjuvant)SCH 900475, Pembrolizumab, KeytrudaCohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475
Cisplatincis-DDP, cis-Platinum II, cis-Diamminedichloroplatinum, DDPCohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475
MK-3475 (adjuvant)SCH 900475, Pembrolizumab, KeytrudaCohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475ExperimentalMK-3475 will be given intravenously 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.
  • MK-3475 (neoadjuvant)
  • Cisplatin
  • MK-3475 (adjuvant)
Cohort 2: Neoadjuvant MK-3475Experimental-MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery
  • MK-3475 (neoadjuvant)
  • 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 ≥ 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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Locoregional recurrence rates in Cohorts 1 and 2
Time Frame:1 year
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Occurrence of adverse events in Cohorts 1 and 2
Time Frame:90 days after last dose of MK-3475
Safety Issue:
Description:Reportable adverse events will be tracked for 30 days following the last day of study treatment. For the purposes of this protocol, reportable adverse events are events thought to be possibly, probably, or definitely related to MK-3475. Events thought to be probably or definitely related to surgery, adjuvant chemotherapy, or radiotherapy need not be recorded. Please note that patients must be followed for events of clinical interest for 90 days following the last day of study treatment.
Measure:Surgical complications and/or delays in Cohorts 1 and 2
Time Frame:At the time of surgery (approximately 2-3 weeks after registration)
Safety Issue:
Description:
Measure:Rate of locoregional recurrences (LRR) in Cohorts 1 and 2
Time Frame:1 year
Safety Issue:
Description:
Measure:Rate of distant metastases (DM) in Cohorts 1 and 2
Time Frame:1 year
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Washington University School of Medicine

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