Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma
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
Conditions: official terms
Carcinoma - Carcinoma, Squamous Cell - Head and Neck Neoplasms
Study Type
Study Phase
Phase 2
Study Design
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: MK-3475 Type: Biological
Name: Surgery Type: Procedure
Name: Intensity modulated radiation therapy Type: Radiation
Name: Image-guided radiation therapy Type: Radiation
Name: Cisplatin Type: Drug
Overall Status
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
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 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 requiring systemic treatment within the past 2 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Patients with hypothyroidism stable on hormone replacement or Sjorgen's syndrome would not be excluded from the study.

- Evidence of interstitial lung disease or 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 active hepatitis B or hepatitis C.

- Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with MK-3475. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
Washington University School of Medicine
St. Louis, Missouri, United States
Status: Recruiting
Contact: Ravindra Uppaluri, M.D., Ph.D. - 314-362-4125 -
Start Date
March 2015
Completion Date
March 2022
Washington University School of Medicine
Washington University School of Medicine
Record processing date processed this data on July 28, 2015 page