Trial Title:
Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma
NCT ID:
NCT02296684
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
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Squamous Cell Carcinoma of Head and Neck
Cisplatin
Pembrolizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
MK-3475 (neoadjuvant)
Arm group label:
Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475
Arm group label:
Cohort 2: Neoadjuvant MK-3475
Other name:
SCH 900475
Other name:
Pembrolizumab
Other name:
Keytruda
Intervention type:
Procedure
Intervention name:
Surgery
Description:
Standard of care
Arm group label:
Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475
Arm group label:
Cohort 2: Neoadjuvant MK-3475
Intervention type:
Radiation
Intervention name:
Intensity modulated radiation therapy
Description:
Recommended, standard of care
Arm group label:
Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475
Arm group label:
Cohort 2: Neoadjuvant MK-3475
Other name:
IMRT
Intervention type:
Radiation
Intervention name:
Image-guided radiation therapy
Description:
Recommended, standard of care
Arm group label:
Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475
Arm group label:
Cohort 2: Neoadjuvant MK-3475
Other name:
IGRT
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Standard of care
Arm group label:
Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475
Arm group label:
Cohort 2: Neoadjuvant MK-3475
Other name:
cis-DDP
Other name:
cis-Platinum II
Other name:
cis-Diamminedichloroplatinum
Other name:
DDP
Intervention type:
Biological
Intervention name:
MK-3475 (adjuvant)
Arm group label:
Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475
Other name:
SCH 900475
Other name:
Pembrolizumab
Other name:
Keytruda
Intervention type:
Procedure
Intervention name:
Peripheral blood
Description:
-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
Arm group label:
Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475
Arm group label:
Cohort 2: Neoadjuvant MK-3475
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.
Criteria for 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).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Dana Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Start date:
March 25, 2015
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Washington University School of Medicine
Agency class:
Other
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Washington University School of Medicine
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT02296684
http://www.siteman.wustl.edu
