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NCT06064097PHASE2Recruiting

A Study Using Nivolumab, in Combination With Chemotherapy Drugs to Treat Nasopharyngeal Carcinoma (NPC)

National Cancer Institute (NCI)

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

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

Interventions

PROCEDURE

Biopsy Procedure

PROCEDURE

Biospecimen Collection

PROCEDURE

Chest Radiography

DRUG

Cisplatin

PROCEDURE

Computed Tomography

PROCEDURE

Echocardiography Test

OTHER

Electronic Health Record Review

OTHER

Fluciclovine F18

DRUG

Gemcitabine

PROCEDURE

Magnetic Resonance Imaging

PROCEDURE

Multigated Acquisition Scan

BIOLOGICAL

Nivolumab

PROCEDURE

Positron Emission Tomography

OTHER

Quality-of-Life Assessment

OTHER

Questionnaire Administration

RADIATION

Radiation Therapy

PROCEDURE

X-Ray Imaging

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Conditions

Stage II Nasopharyngeal Carcinoma AJCC v8Stage III Nasopharyngeal Carcinoma AJCC v8Stage IV Nasopharyngeal Carcinoma AJCC v8

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