Cisplatin, Intensity-Modulated Radiation Therapy, and Pembrolizumab in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma
A Phase I and Expansion Cohort Study of Adjuvant Cisplatin, Intensity-Modulated Radiotherapy, and MK-3475 (Pembrolizumab) in High-Risk Head and Neck Squamous Cell Carcinoma (HNSCC)
3 other identifiers
interventional
37
1 country
69
Brief Summary
This phase I trial studies the side effects and best dose of pembrolizumab when given together with cisplatin and intensity-modulated radiation therapy, in treating patients with stage III-IV squamous cell carcinoma of the head and neck. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Intensity-modulated radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving pembrolizumab with cisplatin and intensity-modulated radiation therapy may work better in treating patients with squamous cell carcinoma of the head and neck.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Nov 2016
Longer than P75 for phase_1
69 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 16, 2016
CompletedFirst Posted
Study publicly available on registry
May 18, 2016
CompletedStudy Start
First participant enrolled
November 28, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 3, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
May 20, 2022
CompletedJune 10, 2022
June 1, 2022
2 years
May 16, 2016
June 9, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
Dose limiting toxicities in patients with high-risk head and neck squamous cell carcinoma treated with adjuvant cisplatin, intensity-modulated radiation therapy, and pembrolizumab
Will be summarized using proportions for binary outcome per cohort.
Up to 4 weeks post intensity-modulated radiation therapy
Secondary Outcomes (9)
Disease free survival
Up to 1 year
Overall survival
Up to 1 year
Local-regional failure
Up to 1 year
Distant metastases
Up to 1 year
Incidence of acute toxicities by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Up to 1 year
- +4 more secondary outcomes
Study Arms (1)
Treatment (cisplatin, pembrolizumab, IMRT)
EXPERIMENTALPatients receive cisplatin IV over 1-2 hours once weekly for weeks 1-6 and pembrolizumab IV over 30 minutes every 3 weeks in weeks 9, 12, 15, 18, and 21. Patients also undergo IMRT in weeks 1-6. Patients may also receive pembrolizumab IV over 30 minutes in weeks 3, 6, 24, and 27.
Interventions
Undergo IMRT
Eligibility Criteria
You may qualify if:
- STEP 1 (REGISTRATION)
- Pathologically (histologically or cytologically) proven diagnosis of head and neck squamous cell carcinoma (HNSCC) involving the oral cavity (excluding lips), oropharynx (p16 negative), hypopharynx or larynx
- Patients must have undergone gross total surgical resection of high-risk oral cavity, oropharynx (p16 negative), larynx, or hypopharynx squamous cell carcinoma (SCC) within 63 days prior to registration; note: patients may have a biopsy under general anesthesia in an operating room followed by definitive ablative cancer surgery representing gross total resection; the gross total resection has to be done within 63 days prior to registration; if, however, patients have ablative resection but demonstrate rapid gross recurrence or are determined to have gross persisting disease requiring re-resection to achieve gross total resection, then the patient is not eligible
- Patients must have at least one of the following high risk pathologic features:
- Extracapsular nodal extension
- Invasive cancer at the primary tumor resection margin (tumor on ink); Note: Patients who have a positive margin and undergo re-resection with final negative margin are eligible only if they can be enrolled within 63 days of initial gross total resection AND extracapsular nodal extension was also present; patients who have a positive margin and undergo re-resection with final negative margin and do not have extracapsular nodal extension, are NOT eligible
- Pathologic stage III or IV HNSCC, including no distant metastases, based on the following minimum diagnostic workup:
- General history/physical examination by a radiation oncologist and/or medical oncologist within 84 days prior to registration
- Examination by an ear nose and throat (ENT) or head \& neck surgeon prior to surgery; a laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure), if appropriate, is recommended but not required; intra-operative examination is acceptable documentation
- Pre-op Imaging of the head and neck: a neck computerized tomography (CT) (with contrast) or CT/positron emission tomography (PET) (with contrast) and/or an magnetic resonance imaging (MRI) of the neck (T1 with gadolinium and T2) within 84 days prior to surgery; note: this imaging data (diagnostic pre-operative scan showing gross disease) is to be submitted in Digital Imaging and Communications in Medicine (DICOM) format via transfer of images and data (TRIAD); the report is to be uploaded into Rave
- Chest imaging with either a CT scan (with or without contrast) or CT/PET (with or without contrast) that includes the chest within 120 days prior to registration; Note: if the CT/PET with or without contrast is done within 84 days prior to surgery, it fulfills the chest imaging requirement
- For patients with oropharyngeal cancer only: the institution will do p16 testing, and if p16 is negative, this tissue must be submitted for central review for confirmation before Step 2 registration; note: if the institution finds that the patient is p16 positive, the patient is excluded from this trial on the basis of distinct biology, prognosis, and low- or intermediate-risk rather than high-risk status
- Zubrod performance status of 0-1 within 28 days prior to registration
- Absolute neutrophil count (ANC): \>= 1,500 /mm\^3
- Platelets: \>= 100,000 / mm\^3
- +14 more criteria
You may not qualify if:
- Definitive clinical or radiologic evidence of metastatic disease
- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years); noninvasive cancers (for example, carcinoma in situ of the breast, oral cavity, or cervix) are permitted even if diagnosed and treated \< 3 years ago
- Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 differentiated thyroid carcinoma, who are eligible
- Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy, or immune therapy for the study cancer; note: prior cytotoxic chemotherapy or biologic/targeted therapy for a different cancer is allowable; however, a prior anti-programmed cell death (PD)-1, anti-PD-L1, or anti-programmed cell death 1 ligand 2 (PD-L2) agent is not permitted
- Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
- Severe, active co-morbidity defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within 6 months prior to registration
- Transmural myocardial infarction within 6 months prior to registration
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; Note: if the infection resolves and the patient is on oral (p.o.) and still within, the required registration timeframe, then the patient is eligible
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
- Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to registration
- History of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease Control and Prevention (CDC) definition; note: human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the cisplatin and IMRT involved in this protocol may be significantly immunosuppressive; patients with known HIV, CD4 counts \>= 250/uL, and undetectable viral loads who are stable on an antiretroviral regimen may be included
- 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 the MK-3475 (pembrolizumab)
- Known history of active TB (Bacillus tuberculosis)
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Cancer Institute (NCI)lead
- NRG Oncologycollaborator
Study Sites (69)
Banner University Medical Center - Tucson
Tucson, Arizona, 85719, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
Sutter Medical Center Sacramento
Sacramento, California, 95816, United States
University of Colorado Hospital
Aurora, Colorado, 80045, United States
Penrose-Saint Francis Healthcare
Colorado Springs, Colorado, 80907, United States
Poudre Valley Hospital
Fort Collins, Colorado, 80524, United States
Yale University
New Haven, Connecticut, 06520, United States
Helen F Graham Cancer Center
Newark, Delaware, 19713, United States
Christiana Care Health System-Christiana Hospital
Newark, Delaware, 19718, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
University of Florida Health Science Center - Gainesville
Gainesville, Florida, 32610, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Grady Health System
Atlanta, Georgia, 30303, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Rush - Copley Medical Center
Aurora, Illinois, 60504, United States
Northwestern University
Chicago, Illinois, 60611, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
Methodist Medical Center of Illinois
Peoria, Illinois, 61636, United States
OSF Saint Francis Medical Center
Peoria, Illinois, 61637, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
Franciscan Health Indianapolis
Indianapolis, Indiana, 46237, United States
Iowa Methodist Medical Center
Des Moines, Iowa, 50309, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, 40202, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121, United States
Henry Ford Cancer Institute-Downriver
Brownstown, Michigan, 48183, United States
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan, 48038, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
The University of Kansas Cancer Center-South
Kansas City, Missouri, 64131, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
Nebraska Methodist Hospital
Omaha, Nebraska, 68114, United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87102, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501, United States
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio, 44111, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Cleveland Clinic Cancer Center Independence
Independence, Ohio, 44131, United States
Cleveland Clinic Cancer Center Mansfield
Mansfield, Ohio, 44906, United States
Hillcrest Hospital Cancer Center
Mayfield Heights, Ohio, 44124, United States
UH Seidman Cancer Center at Lake Health Mentor Campus
Mentor, Ohio, 44060, United States
North Coast Cancer Care
Sandusky, Ohio, 44870, United States
Cleveland Clinic Cancer Center Strongsville
Strongsville, Ohio, 44136, United States
Cleveland Clinic Wooster Family Health and Surgery Center
Wooster, Ohio, 44691, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Clackamas Radiation Oncology Center
Clackamas, Oregon, 97015, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Saint Luke's University Hospital-Bethlehem Campus
Bethlehem, Pennsylvania, 18015, United States
Christiana Care Health System-Concord Health Center
Chadds Ford, Pennsylvania, 19317, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
UPMC-Shadyside Hospital
Pittsburgh, Pennsylvania, 15232, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
PeaceHealth Saint Joseph Medical Center
Bellingham, Washington, 98225, United States
University of Washington Medical Center - Montlake
Seattle, Washington, 98195, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Julie E Bauman
NRG Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 16, 2016
First Posted
May 18, 2016
Study Start
November 28, 2016
Primary Completion
December 3, 2018
Study Completion
May 20, 2022
Last Updated
June 10, 2022
Record last verified: 2022-06