A Study Using Nivolumab, in Combination With Chemotherapy Drugs to Treat Nasopharyngeal Carcinoma (NPC)
Start Date
6/25/2024
Completion Date
12/31/2026
Summary
This phase II trial tests effects of nivolumab in combination with chemotherapy drugs prior to radiation therapy patients with nasopharyngeal carcinoma (NPC). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as gemcitabine and 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. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Researchers want to find out what effects, good and/or bad, adding nivolumab to chemotherapy has on patients with newly diagnosed NPC. In addition, they want to find out if children with NPC may be treated with less radiation therapy and whether this decreases the side effects of therapy.
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate safety of combining chemotherapy (cisplatin and gemcitabine) with an anti-PD1 immune checkpoint inhibitor (nivolumab) in children, adolescents and young adults with nasopharyngeal carcinoma (NPC) by determining the rate of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher immune related adverse events (irAEs). SECONDARY OBJECTIVES: I. To estimate the 2-year event-free survival (EFS) of children, adolescents and young adults with NPC who are treated with induction chemoimmunotherapy (CIT), followed by consolidation chemoradioimmunotherapy (CRIT, cisplatin, nivolumab and response-adjusted, dose de-escalated radiation therapy), and nivolumab maintenance therapy. II. To evaluate the objective response rate (ORR) including complete responders and partial responders (complete response \[CR\] + partial response \[PR\]) of neoadjuvant CIT. III. To evaluate feasibility of combining chemotherapy (cisplatin and gemcitabine) with an anti-PD1 immune checkpoint inhibitor (nivolumab) in children, adolescents and young adults with nasopharyngeal carcinoma (NPC). IV. To evaluate the cumulative incidence of local and distant relapse. EXPLORATORY OBJECTIVES: I. To estimate 5-year EFS and overall survival (OS) of children with NPC who are treated with induction CIT followed by consolidation CRIT, and nivolumab maintenance therapy. II. To compare response assessed by fludeoxyglucose F18 (FDG) positron emission tomography (PET) versus magnetic resonance imaging (MRI). III. To determine treatment outcomes for patients treated with radiation per protocol versus (vs) deviation. IV. To evaluate outcomes comparing patients receiving intensity modulated radiation therapy (IMRT) to proton therapy. V. To objectively measure both acute and long-term toxicity including immune related adverse events and radiation late effects. VI. To evaluate swallowing dysfunction using patient reported outcome (PRO) measures for children and adults throughout the protocol for up to 5 years. VII. To evaluate quality of life (QOL) using Patient-Reported Outcomes Measurement Information System (PROMIS) multidimensional questionnaire throughout the protocol for up to 5 years. VIII. To correlate the lymphocyte to monocyte ratio on complete blood counts (CBCs) with treatment response and outcomes. IX. To collect and bank specimens (including tumor, blood and stool) for future research studies. OUTLINE: INDUCTION THERAPY: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 of each cycle, gemcitabine IV over 30 minutes on days 1 and 8 of each cycle, and cisplatin IV over 3-6 hours on day 1 of each cycle. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: Patients receive nivolumab IV over 30 minutes on day 1 of each cycle and cisplatin IV over 3-6 hours on day 1 of cycles 1-2. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive concurrent radiation therapy on trial. MAINTENANCE THERAPY: Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening and as clinically indicated on trial. Patients undergo MRI, FDG PET, and computed tomography (CT) throughout the trial and chest x-ray during follow-up. Patients also undergo dental x-ray imaging on the trial. Patients may optionally undergo tissue biopsy, blood and stool sample collection during screening and on trial. After completion of study treatment, patients are followed up every 3 months for 12 months, every 6 months until 24 months off therapy, and then yearly until 5 years off therapy.
Eligibility Criteria
Age Range: No minimum to 21 years
Interventions
Biopsy Procedure
Biospecimen Collection
Chest Radiography
Cisplatin
Computed Tomography
Echocardiography Test
Electronic Health Record Review
Fluciclovine F18
Gemcitabine
Magnetic Resonance Imaging
Multigated Acquisition Scan
Nivolumab
Positron Emission Tomography
Quality-of-Life Assessment
Questionnaire Administration
Radiation Therapy
X-Ray Imaging
Conditions
Locations
Children's Hospital of Alabama
Birmingham, Alabama 35233
United States
Phoenix Childrens Hospital
Phoenix, Arizona 85016
United States
Arkansas Children's Hospital
Little Rock, Arkansas 72202-3591
United States
Kaiser Permanente Downey Medical Center
Downey, California 90242
United States
Loma Linda University Medical Center
Loma Linda, California 92354
United States
Children's Hospital Los Angeles
Los Angeles, California 90027
United States
Valley Children's Hospital
Madera, California 93636
United States
UCSF Benioff Children's Hospital Oakland
Oakland, California 94609
United States
Kaiser Permanente-Oakland
Oakland, California 94611
United States
Rady Children's Hospital - San Diego
San Diego, California 92123
United States
UCSF Medical Center-Mission Bay
San Francisco, California 94158
United States
Children's Hospital Colorado
Aurora, Colorado 80045
United States
Connecticut Children's Medical Center
Hartford, Connecticut 06106
United States
Alfred I duPont Hospital for Children
Wilmington, Delaware 19803
United States
Children's National Medical Center
Washington D.C., District of Columbia 20010
United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida 32610
United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida 32207
United States
Nicklaus Children's Hospital
Miami, Florida 33155
United States
Arnold Palmer Hospital for Children
Orlando, Florida 32806
United States
Nemours Children's Hospital
Orlando, Florida 32827
United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida 32504
United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida 33607
United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia 30329
United States
Lurie Children's Hospital-Chicago
Chicago, Illinois 60611
United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois 60637
United States
Riley Hospital for Children
Indianapolis, Indiana 46202
United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky 40536
United States
Children's Hospital New Orleans
New Orleans, Louisiana 70118
United States
Maine Children's Cancer Program
Scarborough, Maine 04074
United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland 21287
United States
Dana-Farber Cancer Institute
Boston, Massachusetts 02215
United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan 49503
United States
Mayo Clinic in Rochester
Rochester, Minnesota 55905
United States
University of Mississippi Medical Center
Jackson, Mississippi 39216
United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri 64108
United States
Washington University School of Medicine
St Louis, Missouri 63110
United States
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska 68114
United States
University of Nebraska Medical Center
Omaha, Nebraska 68198
United States
Hackensack University Medical Center
Hackensack, New Jersey 07601
United States
Jersey Shore Medical Center
Neptune City, New Jersey 07753
United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey 08903
United States
Newark Beth Israel Medical Center
Newark, New Jersey 07112
United States
Albany Medical Center
Albany, New York 12208
United States
Montefiore Medical Center - Moses Campus
The Bronx, New York 10467
United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina 28203
United States
Duke University Medical Center
Durham, North Carolina 27710
United States
East Carolina University
Greenville, North Carolina 27834
United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina 27157
United States
Sanford Broadway Medical Center
Fargo, North Dakota 58122
United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio 45229
United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio 44106
United States
Nationwide Children's Hospital
Columbus, Ohio 43205
United States
Dayton Children's Hospital
Dayton, Ohio 45404
United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania 18103
United States
Penn State Children's Hospital
Hershey, Pennsylvania 17033
United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania 19104
United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania 15224
United States
Prisma Health Richland Hospital
Columbia, South Carolina 29203
United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina 29605
United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota 57117-5134
United States
Saint Jude Children's Research Hospital
Memphis, Tennessee 38105
United States
The Children's Hospital at TriStar Centennial
Nashville, Tennessee 37203
United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee 37232
United States
Dell Children's Medical Center of Central Texas
Austin, Texas 78723
United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas 75390
United States
Cook Children's Medical Center
Fort Worth, Texas 76104
United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas 77030
United States
UT MD Anderson Cancer Center
Houston, Texas 77030
United States
Children's Hospital of San Antonio
San Antonio, Texas 78207
United States
University of Virginia Cancer Center
Charlottesville, Virginia 22908
United States
Children's Hospital of The King's Daughters
Norfolk, Virginia 23507
United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia 23298
United States
Seattle Children's Hospital
Seattle, Washington 98105
United States
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington 98405
United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin 53226
United States
Alberta Children's Hospital
Calgary, Alberta T3B 6A8
Canada
University of Alberta Hospital
Edmonton, Alberta T6G 2B7
Canada
Hospital for Sick Children
Toronto, Ontario M5G 1X8
Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec H3H 1P3
Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec H3T 1C5
Canada
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec J1H 5N4
Canada
Starship Children's Hospital
Grafton, Auckland 1145
New Zealand
Christchurch Hospital
Christchurch, 8011
New Zealand
University Pediatric Hospital
San Juan, 00926
Puerto Rico