A Phase 2 Study Using Chemoimmunotherapy With Gemcitabine, Cisplatin and Nivolumab in Newly Diagnosed Nasopharyngeal Carcinoma (NPC)
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.
Arms & interventions
- ProcedureBiopsy Procedure
Undergo tissue biopsy
- ProcedureBiospecimen Collection
Undergo blood and stool sample collection
- ProcedureChest Radiography
Undergo chest x-ray
- DrugCisplatin
Given IV
- ProcedureComputed Tomography
Undergo CT
- ProcedureEchocardiography Test
Undergo ECHO
- OtherElectronic Health Record Review
Ancillary studies
- OtherFluciclovine F18
Given IV
- DrugGemcitabine
Given IV
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- ProcedureMultigated Acquisition Scan
Undergo MUGA
- BiologicalNivolumab
Given IV
- ProcedurePositron Emission Tomography
Undergo PET
- OtherQuality-of-Life Assessment
Ancillary studies
- OtherQuestionnaire Administration
Ancillary studies
- RadiationRadiation Therapy
Receive radiation therapy
- ProcedureX-Ray Imaging
Undergo dental x-ray
Outcome measures
Primary
Incidence of grade 3 or higher immune-related adverse events (irAE) during induction chemoimmunotherapy (CIT)
Will be assessed by Common Terminology Criteria for Adverse Events. IrAEs include diarrhea (noninfectious), colitis (noninfectious), pneumonitis (noninfectious), myocarditis, elevated alanine aminotransferase, elevated aspartate aminotransferase, pancreatitis, elevated blood bilirubin, hypophysitis and hyperthyroid considered possibly, probably, or definitely related to nivolumab.
Time frame: Until the end of consolidation therapy
Secondary
Event-free survival (EFS)
Time frame: From date of enrollment to the earliest occurrence of date of relapse, disease progression, second malignant neoplasm or death due to any cause, assessed at 2 years
Objective response rate
Time frame: At the end of induction CIT
Feasibility success of the induction regimen
Time frame: At the end of induction CIT
Cumulative incidence of local or distant relapse
Time frame: Up to 5 years
Eligibility criteria
Study locations (76)
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591
Kaiser Permanente Downey Medical Center
Downey, California, 90242
Loma Linda University Medical Center
Loma Linda, California, 92354
Children's Hospital Los Angeles
Los Angeles, California, 90027
Valley Children's Hospital
Madera, California, 93636
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Kaiser Permanente-Oakland
Oakland, California, 94611
Rady Children's Hospital - San Diego
San Diego, California, 92123
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Children's Hospital Colorado
Aurora, Colorado, 80045
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Children's National Medical Center
Washington D.C., District of Columbia, 20010
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Nicklaus Children's Hospital
Miami, Florida, 33155
Arnold Palmer Hospital for Children
Orlando, Florida, 32806
Nemours Children's Hospital
Orlando, Florida, 32827
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Riley Hospital for Children
Indianapolis, Indiana, 46202
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Children's Hospital New Orleans
New Orleans, Louisiana, 70118
Maine Children's Cancer Program
Scarborough, Maine, 04074
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
Washington University School of Medicine
St Louis, Missouri, 63110
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Jersey Shore Medical Center
Neptune City, New Jersey, 07753
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903
Newark Beth Israel Medical Center
Newark, New Jersey, 07112
Albany Medical Center
Albany, New York, 12208
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Duke University Medical Center
Durham, North Carolina, 27710
East Carolina University
Greenville, North Carolina, 27834
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
Nationwide Children's Hospital
Columbus, Ohio, 43205
Dayton Children's Hospital
Dayton, Ohio, 45404
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, 18103
Penn State Children's Hospital
Hershey, Pennsylvania, 17033
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Prisma Health Richland Hospital
Columbia, South Carolina, 29203
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Cook Children's Medical Center
Fort Worth, Texas, 76104
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
UT MD Anderson Cancer Center
Houston, Texas, 77030
Children's Hospital of San Antonio
San Antonio, Texas, 78207
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Seattle Children's Hospital
Seattle, Washington, 98105
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226