The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02296684
Recruitment Status : Active, not recruiting
First Posted : November 20, 2014
Results First Posted : May 11, 2023
Last Update Posted : April 25, 2024
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Washington University School of Medicine

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief 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.

Condition or disease Intervention/treatment Phase
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 Biological: MK-3475 (neoadjuvant) Procedure: Surgery Radiation: Intensity modulated radiation therapy Radiation: Image-guided radiation therapy Drug: Cisplatin Biological: MK-3475 (adjuvant) Procedure: Peripheral blood Phase 2

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 67 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Immunotherapy With MK-3475 in Locoregionally Advanced, Surgically Resectable Head and Neck Squamous Cell Carcinoma
Actual Study Start Date : March 25, 2015
Actual Primary Completion Date : April 5, 2022
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475
  • MK-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 surgical pathology from standard of care surgery. 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.
 Biological: MK-3475 (neoadjuvant)
Other Names:
  • SCH 900475
  • Pembrolizumab
  • Keytruda

Procedure: Surgery
Standard of care

Radiation: Intensity modulated radiation therapy
Recommended, standard of care
Other Name: IMRT

Radiation: Image-guided radiation therapy
Recommended, standard of care
Other Name: IGRT

Drug: Cisplatin
Standard of care
Other Names:
  • cis-DDP
  • cis-Platinum II
  • cis-Diamminedichloroplatinum
  • DDP

Biological: MK-3475 (adjuvant)
Other Names:
  • SCH 900475
  • Pembrolizumab
  • Keytruda

Procedure: Peripheral blood
-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)
 Biological: MK-3475 (neoadjuvant)
Other Names:
  • SCH 900475
  • Pembrolizumab
  • Keytruda

Procedure: Surgery
Standard of care

Radiation: Intensity modulated radiation therapy
Recommended, standard of care
Other Name: IMRT

Radiation: Image-guided radiation therapy
Recommended, standard of care
Other Name: IGRT

Drug: Cisplatin
Standard of care
Other Names:
  • cis-DDP
  • cis-Platinum II
  • cis-Diamminedichloroplatinum
  • DDP

Procedure: Peripheral blood
-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


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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) ]
    -The percentage of participants who developed local-regional recurrence within one year of surgery

  2. 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) ]
    -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.

  3. 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) ]
    • Major pathologic treatment effect=pathologic tumor response (pTR).
    • pTR was defined as the presence of tumor cell necrosis and keratinous debris with giant cell/histiocytic reaction, quantified as a percentage of the overall tumor bed (area pathologic response/area pathologic response plus viable tumor): pTR-0 (>10%), pTR-1 (10-49%), and pTR-2 (≥50%).

  4. 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) ]
    • Major pathologic treatment effect=pathologic tumor response (pTR).
    • pTR was defined as the presence of tumor cell necrosis and keratinous debris with giant cell/histiocytic reaction, quantified as a percentage of the overall tumor bed (area pathologic response/area pathologic response plus viable tumor): pTR-0 (>10%), pTR-1 (10-49%), and pTR-2 (≥50%).


Secondary Outcome Measures :
  1. Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events [ Time Frame: Through 30 days after last dose of MK-3475 ]
    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.

  2. 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) ]
  3. Locoregional Recurrence Rates in Cohorts 1 and 2 [ Time Frame: Through completion of follow-up (estimated to be 5 years after treatment) ]
  4. Rate of Distant Metastases (DM) in Cohorts 1 and 2 [ Time Frame: Through completion of follow-up (estimated to be 5 years after treatment) ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02296684


Locations
Layout table for location information
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Washington University School of Medicine
Merck Sharp & Dohme LLC
Investigators
Layout table for investigator information
Principal Investigator: Douglas R Adkins, M.D. Washington University School of Medicine
  Study Documents (Full-Text)

Documents provided by Washington University School of Medicine:
Study Protocol and Statistical Analysis Plan  [PDF] October 5, 2018

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02296684    
Other Study ID Numbers: 201412118
First Posted: November 20, 2014    Key Record Dates
Results First Posted: May 11, 2023
Last Update Posted: April 25, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
 Neoplasms by Site
Cisplatin
Pembrolizumab
Antineoplastic Agents
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action