- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02296684
Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma
April 19, 2023 updated by: Washington University School of Medicine
Immunotherapy With MK-3475 in Locoregionally Advanced, Surgically Resectable Head and Neck Squamous Cell Carcinoma
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.
Study Overview
Status
Active, not recruiting
Conditions
Study Type
Interventional
Enrollment (Actual)
67
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Dana Farber Cancer Institute
-
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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New York
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New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475
|
Other Names:
Standard of care
Recommended, standard of care
Other Names:
Recommended, standard of care
Other Names:
Standard of care
Other Names:
Other Names:
-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
|
Experimental: Cohort 2: Neoadjuvant MK-3475
-MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery)
|
Other Names:
Standard of care
Recommended, standard of care
Other Names:
Recommended, standard of care
Other Names:
Standard of care
Other Names:
-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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Locoregional Recurrence Rates in Cohorts 1 and 2
Time Frame: Within 1 year of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose)
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-The percentage of participants who developed local-regional recurrence within one year of surgery
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Within 1 year of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose)
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Distant Failure Rate in Cohorts 1 and 2
Time Frame: Within 1 year of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose)
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-The percentage of participants who developed distant failure within one year of surgery.
Distant disease is cancer that is found in another part of the body that is far away from where the original (primary) tumor first formed.
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Within 1 year of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose)
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Rate of Major Pathologic Treatment Effect in Cohort 1
Time Frame: At the time of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose)
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At the time of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose)
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Rate of Major Pathologic Treatment Effect in Cohort 2
Time Frame: At the time of surgery (surgery occurred within 13-22 days after last neoadjuvant MK-3475 dose)
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At the time of surgery (surgery occurred within 13-22 days after last neoadjuvant MK-3475 dose)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events
Time Frame: Through 30 days after last dose of MK-3475
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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.
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Through 30 days after last dose of MK-3475
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Number of Surgical Complications and/or Delays in Cohorts 1 and 2
Time Frame: At the time of surgery (approximately 2-3 weeks after registration)
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At the time of surgery (approximately 2-3 weeks after registration)
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Locoregional Recurrence Rates in Cohorts 1 and 2
Time Frame: Through completion of follow-up (estimated to be 5 years after treatment)
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Through completion of follow-up (estimated to be 5 years after treatment)
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Rate of Distant Metastases (DM) in Cohorts 1 and 2
Time Frame: Through completion of follow-up (estimated to be 5 years after treatment)
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Through completion of follow-up (estimated to be 5 years after treatment)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Douglas R Adkins, M.D., Washington University School of Medicine
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 25, 2015
Primary Completion (Actual)
April 5, 2022
Study Completion (Anticipated)
December 31, 2025
Study Registration Dates
First Submitted
November 17, 2014
First Submitted That Met QC Criteria
November 18, 2014
First Posted (Estimate)
November 20, 2014
Study Record Updates
Last Update Posted (Estimate)
May 11, 2023
Last Update Submitted That Met QC Criteria
April 19, 2023
Last Verified
April 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Neoplasms, Squamous Cell
- Head and Neck Neoplasms
- Carcinoma
- Carcinoma, Squamous Cell
- Squamous Cell Carcinoma of Head and Neck
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Cisplatin
- Pembrolizumab
Other Study ID Numbers
- 201412118
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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