Cancerify Logo
Log inSign up
Back to clinical trials
RecruitingInterventionalPhase 2

A Phase 2 Study Using Chemoimmunotherapy With Gemcitabine, Cisplatin and Nivolumab in Newly Diagnosed Nasopharyngeal Carcinoma (NPC)

NCT ID: NCT06064097Sponsor: National Cancer Institute (NCI)Last updated: 2026-06-17

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

Sex: AllAge: Up to 21 YearsHealthy volunteers: No
Inclusion Criteria: * Patients must be ≤ 21 years of age at the time of study enrollment * Newly diagnosed American Joint Committee on Cancer (AJCC) stage II-IV nasopharyngeal carcinoma (NPC) * Patients must have had histologic verification of the malignancy at original diagnosis * Although submission of tumor tissue for the molecular characterization initiative is not required for eligibility, it is strongly recommended * Patients must have had histologic verification of the malignancy at original diagnosis * Although submission of tumor tissue for the molecular characterization initiative is not required for eligibility, it is strongly recommended * Patients must have a Lansky (for patients ≤ 16 years of age) or Karnofsky (for patients \> 16 years of age) performance status score of ≥ 60% * Peripheral absolute neutrophil count (ANC) ≥ 1000/uL (within 7 days prior to start of protocol therapy) * Platelet count ≥ 100,000/uL (transfusion independent) (within 7 days prior to start of protocol therapy) * Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2 or (within 7 days prior to start of protocol therapy) * A serum creatinine based on age/sex (within 7 days prior to start of protocol therapy) Age: Maximum serum creatinine (mg/dL) 1 month to \< 6 months: 0.4 mg/dL (male); 0.4 mg/dL (female) 6 months to \< 1 year: 0.5 mg/dL (male); 0.5 mg/dL (female) 1 to \< 2 years: 0.6 mg/dL (male); 0.6 mg/dL (female) 2 to \< 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female) 6 to \< 10 years 1 mg/dL (male); 1 mg/dL (female) 10 to \<13 years: 1.2 mg/dL (male); 1.2 mg/dL (female) 13 to \< 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female) ≥ 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female) * Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, and (within 7 days prior to start of protocol therapy) * Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) ≤ 135 U/L\* (within 7 days prior to start of protocol therapy) * Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L * Shortening fraction of ≥ 27% by echocardiogram, or * Ejection fraction of ≥ 50% by radionuclide angiogram * No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \> 94% if there is clinical indication for determination * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months and T-cell count above the lower limit of normal are eligible for this trial * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load Exclusion Criteria: * Patients who received prior radiotherapy to the head or neck * Patients who received prior chemotherapy or radiation for the treatment of any cancer in the last 3 years. These patients must also be in remission * Patients with a diagnosis of immunodeficiency * Patients with 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 agents). 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. * Note: Patients with well-controlled asthma and no need for systemic steroids for the treatment of asthma in the last 12 months will not be excluded * Patients with a condition requiring systemic treatment with either corticosteroids (\> 0.25 mg/kg (10 mg) daily prednisone equivalent) within 14 days or other immunosuppressive medications within 30 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses \> 0.25 mg/kg (10 mg) daily prednisone equivalent, are permitted in the absence of active autoimmune disease * Patients with a history of (non-infectious) pneumonitis that required steroids or current pneumonitis * Patients with detectable viral load of human immunodeficiency virus (HIV), hepatitis B or hepatitis C, or active tuberculosis * Patients who have undergone solid organ or allogeneic hematopoietic transplant at any time * Due to risks of fetal and teratogenic adverse events as seen in animal studies, a negative pregnancy test must be obtained in females of childbearing potential, defined as females who are post-menarchal. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Females of childbearing potential that are sexually active must agree to either practice 2 medically accepted highly-effective methods of contraception at the same time or abstain from heterosexual intercourse from the time of signing the informed consent through 5 months after the last dose of nivolumab, 6 months after the last dose of gemcitabine, and 14 months after the last dose of cisplatin, whichever is longer * Males of childbearing potential that are sexually active must agree to either practice a medically accepted highly-effective methods of contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 3 months after the last dose of gemcitabine, and 11 months after the last dose of cisplatin, whichever is longer * Lactating females are not eligible unless they have agreed not to breastfeed their infants starting with the first dose of study therapy through 5 months after the last dose of nivolumab * All patients and/or their parents or legal guardians must sign a written informed consent * All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Study locations (76)

Children's Hospital of Alabama

Birmingham, Alabama, 35233

Recruiting
Site Public Contact · Contact
Jamie M. Aye · Principal Investigator

Phoenix Childrens Hospital

Phoenix, Arizona, 85016

Recruiting
Site Public Contact · Contact
Alok K. Kothari · Principal Investigator

Arkansas Children's Hospital

Little Rock, Arkansas, 72202-3591

Recruiting
Site Public Contact · Contact
Michael W. Bishop · Principal Investigator

Kaiser Permanente Downey Medical Center

Downey, California, 90242

Recruiting
Site Public Contact · Contact
Robert M. Cooper · Principal Investigator

Loma Linda University Medical Center

Loma Linda, California, 92354

Recruiting
Site Public Contact · Contact
Albert Kheradpour · Principal Investigator

Children's Hospital Los Angeles

Los Angeles, California, 90027

Recruiting
Site Public Contact · Contact
Rachana Shah · Principal Investigator

Valley Children's Hospital

Madera, California, 93636

Recruiting
Site Public Contact · Contact
Ruetima Titapiwatanakun · Principal Investigator

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609

Recruiting
Site Public Contact · Contact
Jennifer G. Michlitsch · Principal Investigator

Kaiser Permanente-Oakland

Oakland, California, 94611

Recruiting
Site Public Contact · Contact
Aarati V. Rao · Principal Investigator

Rady Children's Hospital - San Diego

San Diego, California, 92123

Recruiting
Site Public Contact · Contact
William D. Roberts · Principal Investigator

UCSF Medical Center-Mission Bay

San Francisco, California, 94158

Recruiting
Site Public Contact · Contact
Arun A. Rangaswami · Principal Investigator

Children's Hospital Colorado

Aurora, Colorado, 80045

Recruiting
Site Public Contact · Contact
Navin R. Pinto · Principal Investigator

Connecticut Children's Medical Center

Hartford, Connecticut, 06106

Recruiting
Site Public Contact · Contact
Michael S. Isakoff · Principal Investigator

Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803

Recruiting
Site Public Contact · Contact
Sridhi Patel · Principal Investigator

Children's National Medical Center

Washington D.C., District of Columbia, 20010

Recruiting
Jeffrey S. Dome · Principal Investigator

UF Health Cancer Institute - Gainesville

Gainesville, Florida, 32610

Recruiting
Site Public Contact · Contact
Brian Stover · Principal Investigator

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, 32207

Recruiting
Site Public Contact · Contact
Sridhi Patel · Principal Investigator

Nicklaus Children's Hospital

Miami, Florida, 33155

Recruiting
Site Public Contact · Contact
Maggie E. Fader · Principal Investigator

Arnold Palmer Hospital for Children

Orlando, Florida, 32806

Recruiting
Jaime M. Libes-Bander · Principal Investigator

Nemours Children's Hospital

Orlando, Florida, 32827

Recruiting
Site Public Contact · Contact
Sridhi Patel · Principal Investigator

Nemours Children's Clinic - Pensacola

Pensacola, Florida, 32504

Recruiting
Site Public Contact · Contact
Jeffrey H. Schwartz · Principal Investigator

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, 33607

Recruiting
Site Public Contact · Contact
Don E. Eslin · Principal Investigator

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329

Suspended

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611

Recruiting
Site Public Contact · Contact
Amy L. Walz · Principal Investigator

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637

Recruiting
Lorraine E. Canham · Principal Investigator

Riley Hospital for Children

Indianapolis, Indiana, 46202

Recruiting
Site Public Contact · Contact
Marissa Just · Principal Investigator

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536

Not Yet Recruiting
Site Public Contact · Contact
James T. Badgett · Principal Investigator

Children's Hospital New Orleans

New Orleans, Louisiana, 70118

Recruiting
Site Public Contact · Contact
Maria C. Velez-Yanguas · Principal Investigator

Maine Children's Cancer Program

Scarborough, Maine, 04074

Recruiting
Site Public Contact · Contact
Aaron R. Weiss · Principal Investigator

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287

Recruiting
Site Public Contact · Contact
Robyn D. Gartrell · Principal Investigator

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting
Site Public Contact · Contact
Allison F. O'Neill · Principal Investigator

Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503

Recruiting
Site Public Contact · Contact
Kathleen Y. Butler · Principal Investigator

Mayo Clinic in Rochester

Rochester, Minnesota, 55905

Recruiting
Site Public Contact · Contact
Peter Schoettler · Principal Investigator

University of Mississippi Medical Center

Jackson, Mississippi, 39216

Recruiting
Site Public Contact · Contact
Amanda Strobel · Principal Investigator

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108

Recruiting
Site Public Contact · Contact
Keith J. August · Principal Investigator

Washington University School of Medicine

St Louis, Missouri, 63110

Recruiting
Site Public Contact · Contact
Frederick S. Huang · Principal Investigator

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, 68114

Recruiting
Site Public Contact · Contact
Jill C. Beck · Principal Investigator

University of Nebraska Medical Center

Omaha, Nebraska, 68198

Recruiting
Site Public Contact · Contact
Jill C. Beck · Principal Investigator

Hackensack University Medical Center

Hackensack, New Jersey, 07601

Recruiting
Site Public Contact · Contact
Katharine Offer · Principal Investigator

Jersey Shore Medical Center

Neptune City, New Jersey, 07753

Recruiting
Site Public Contact · Contact
Katharine Offer · Principal Investigator

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08903

Recruiting
Site Public Contact · Contact
Scott Moerdler · Principal Investigator

Newark Beth Israel Medical Center

Newark, New Jersey, 07112

Recruiting
Site Public Contact · Contact
Teena Bhatla · Principal Investigator

Albany Medical Center

Albany, New York, 12208

Recruiting
Site Public Contact · Contact
Lauren R. Weintraub · Principal Investigator

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467

Recruiting
Site Public Contact · Contact
Alice Lee · Principal Investigator

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203

Recruiting
Site Public Contact · Contact
Joel A. Kaplan · Principal Investigator

Duke University Medical Center

Durham, North Carolina, 27710

Recruiting
Site Public Contact · Contact
Jessica M. Sun · Principal Investigator

East Carolina University

Greenville, North Carolina, 27834

Recruiting
Site Public Contact · Contact
Andrea R. Whitfield · Principal Investigator

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157

Recruiting
Site Public Contact · Contact
Sarah Supples · Principal Investigator

Sanford Broadway Medical Center

Fargo, North Dakota, 58122

Recruiting
Samuel J. Milanovich · Principal Investigator

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229

Recruiting
Site Public Contact · Contact
Brian K. Turpin · Principal Investigator

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, 44106

Recruiting
Site Public Contact · Contact
Duncan S. Stearns · Principal Investigator

Nationwide Children's Hospital

Columbus, Ohio, 43205

Recruiting
Mark A. Ranalli · Principal Investigator

Dayton Children's Hospital

Dayton, Ohio, 45404

Recruiting
Site Public Contact · Contact
Jordan M. Wright · Principal Investigator

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104

Recruiting
Site Public Contact · Contact
Rene Y. McNall-Knapp · Principal Investigator

Lehigh Valley Hospital-Cedar Crest

Allentown, Pennsylvania, 18103

Recruiting
Site Public Contact · Contact
Jacob A. Troutman · Principal Investigator

Penn State Children's Hospital

Hershey, Pennsylvania, 17033

Recruiting
Site Public Contact · Contact
Lisa M. McGregor · Principal Investigator

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104

Recruiting
Site Public Contact · Contact
Theodore W. Laetsch · Principal Investigator

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224

Recruiting
Site Public Contact · Contact
Brittani K. Seynnaeve · Principal Investigator

Prisma Health Richland Hospital

Columbia, South Carolina, 29203

Recruiting
Site Public Contact · Contact
Stuart L. Cramer · Principal Investigator

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, 29605

Recruiting
Site Public Contact · Contact
Aniket Saha · Principal Investigator

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, 57117-5134

Recruiting
Kayelyn J. Wagner · Principal Investigator

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105

Recruiting
Site Public Contact · Contact
Catherine G. Lam · Principal Investigator

The Children's Hospital at TriStar Centennial

Nashville, Tennessee, 37203

Recruiting
Site Public Contact · Contact
Clinton M. Carroll · Principal Investigator

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232

Recruiting
Site Public Contact · Contact
Scott C. Borinstein · Principal Investigator

Dell Children's Medical Center of Central Texas

Austin, Texas, 78723

Recruiting
Shannon M. Cohn · Principal Investigator

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390

Recruiting
Avanthi T. Shah · Principal Investigator

Cook Children's Medical Center

Fort Worth, Texas, 76104

Recruiting
Chelsee Greer · Principal Investigator

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030

Recruiting
Site Public Contact · Contact
Mehmet F. Okcu · Principal Investigator

UT MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting
Site Public Contact · Contact
Najat C. Daw · Principal Investigator

Children's Hospital of San Antonio

San Antonio, Texas, 78207

Recruiting
Site Public Contact · Contact
Julie Voeller · Principal Investigator

University of Virginia Cancer Center

Charlottesville, Virginia, 22908

Recruiting
Brian C. Belyea · Principal Investigator

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507

Recruiting
Site Public Contact · Contact
Melissa S. Mark · Principal Investigator

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298

Recruiting
Site Public Contact · Contact
Madhu S. Gowda · Principal Investigator

Seattle Children's Hospital

Seattle, Washington, 98105

Recruiting
Site Public Contact · Contact
Sarah E. Leary · Principal Investigator

Mary Bridge Children's Hospital and Health Center

Tacoma, Washington, 98405

Recruiting
Site Public Contact · Contact
Robert G. Irwin · Principal Investigator

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226

Recruiting
Site Public Contact · Contact
Angela Steineck · Principal Investigator