Testing Nivolumab and Ipilimumab Immunotherapy With or Without the Targeted Drug Cabozantinib in Recurrent, Metastatic, or Incurable Nasopharyngeal Cancer
Randomized Phase 2 Study of Nivolumab and Ipilimumab With or Without Cabozantinib in Patients With Advanced Nasopharyngeal Carcinoma That Have Progressed After Platinum Treatment and Immunotherapy
3 other identifiers
interventional
50
1 country
92
Brief Summary
This phase II trial tests how well nivolumab and ipilimumab immunotherapy with or without cabozantinib works in treating patients with nasopharyngeal cancer that has come back (after a period of improvement) (recurrent), has spread from where it first started (primary site) to other places in the body (metastatic), or for which no treatment is currently available (incurable). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving immunotherapy with nivolumab and ipilimumab and targeted therapy with cabozantinib may help shrink and stabilize nasopharyngeal cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Feb 2024
Typical duration for phase_2
92 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
June 13, 2023
CompletedFirst Posted
Study publicly available on registry
June 15, 2023
CompletedStudy Start
First participant enrolled
February 19, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 16, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 16, 2028
June 12, 2026
March 1, 2026
4.3 years
June 13, 2023
June 11, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free survival (PFS)
PFS will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.
From randomization to the first of either progression or death from any cause, or censored at last known tumor assessment date, assessed up to 2 years
Secondary Outcomes (5)
Overall survival (OS)
From randomization to death from any cause, or censored at last known follow-up, assessed up to 2 years
Incidence of adverse events
Up to 2 years
Response by subgroups of interest
Up to 2 years
ORR
Up to 2 years
Predictors of response
Up to 2 years
Study Arms (2)
Arm A (nivolumab, ipilimumab)
ACTIVE COMPARATORPatients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI and collection of blood samples throughout the trial.
Arm B (nivolumab, ipilimumab, cabozantinib)
EXPERIMENTALPatients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 and cabozantinib S-malate PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may continue with cabozantinib S-malate after 2 years per treating investigator. Patients undergo CT or MRI and collection of blood samples throughout the trial.
Interventions
Undergo MRI
Given PO
Undergo collection of blood samples
Undergo CT scan
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have histologically documented nasopharyngeal carcinoma (NPC) regardless of World Health Organization (WHO) classification (keratinizing squamous cell carcinoma, non-keratinizing, or basaloid squamous cell carcinoma) and regardless of association with Epstein-Barr virus (EBV) and/or human papillomavirus (HPV)
- Recurrent, metastatic and incurable disease treated with platinum-gemcitabine and prior PD-1/L1 blockade (as first or second-line therapy) where immunotherapy was part of the most recent prior line of therapy
- Patients are eligible regardless of prior smoking history, p16 immunohistochemistry (IHC) status, PD-L1 expression status, EBV tumor status, EBV viral load at baseline, or tumor genomic alteration status
- Patients must have at least one measurable lesion (by RECIST v1.1) which has not been previously irradiated that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions as \>= 10 mm (\>= 1 cm) (and short axis for nodal lesions, LN \>= 15 mm) with CT scan, MRI, or calipers by clinical exam
- Patients may have had no more than 2 prior lines of prior systemic therapy for recurrent, metastatic NPC
- No prior VEGFR targeted therapy permitted
- Age \>= 18 years
- Eastern Cooperative Oncology Group Performance (ECOG) performance status 0-2
- Absolute neutrophil count (ANC) \>= 1,000/mm\^3
- Hemoglobin \>= 9 g/dL
- Platelet count \>= 100,000/mm\^3
- Creatinine or creatinine clearance =\< 1.5 mg/dL or \>= 30 Modification of Diet in Renal Disease (MDRD)
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN); except subjects with Gilbert syndrome who can have a total bilirubin \< 3 mg/dL
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGT\]) =\< 3 x upper limit of normal (ULN)
- Up to =\< 5 allowed with liver metastases
- +3 more criteria
You may not qualify if:
- No chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration. Palliative (limited-field) radiation therapy is permitted, if all of the following criteria are met:
- Repeat imaging demonstrates no new sites of bone metastases.
- The lesion being considered for palliative radiation is not a target lesion
- No patients with a prior malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
- Brain metastases allowed: Patients with treated brain metastases are eligible if follow-up brain imaging 3 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression. Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
- For patients with evidence of chronic hepatitis B (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 receiving treatment, they are eligible if they have an undetectable HCV viral load
- Solid organ or tissue transplant is allowed: - subsequent therapy with nivolumab increases the risk of organ/tissue rejection. Patients must be instructed that it is crucial they stay in touch with their transplant team during treatment
- No active autoimmune disease: or history of autoimmune disease that might recur, and which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include but are not limited to patients with a history of
- Immune related neurologic disease,
- Multiple sclerosis,
- Autoimmune (demyelinating) neuropathy,
- Guillain-Barre syndrome (GBS),
- Myasthenia gravis;
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (92)
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612, United States
Keck Medicine of USC Koreatown
Los Angeles, California, 90020, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
USC Norris Oncology/Hematology-Newport Beach
Newport Beach, California, 92663, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, 94304, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706, United States
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605, United States
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814, United States
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687, United States
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854, United States
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, 83864, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Illinois
Chicago, Illinois, 60612, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Carle at The Riverfront
Danville, Illinois, 61832, United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115, United States
Carle Physician Group-Effingham
Effingham, Illinois, 62401, United States
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201, United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134, United States
NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois, 60026, United States
Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois, 60026, United States
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois, 60030, United States
Ingalls Memorial Hospital
Harvey, Illinois, 60426, United States
NorthShore University HealthSystem-Highland Park Hospital
Highland Park, Illinois, 60035, United States
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, 60045, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451, United States
Northwestern Medicine Orland Park
Orland Park, Illinois, 60462, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023, United States
Mercy Cancer Center-West Lakes
Clive, Iowa, 50325, United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325, United States
Heartland Oncology and Hematology LLP
Council Bluffs, Iowa, 51503, United States
Methodist Jennie Edmundson Hospital
Council Bluffs, Iowa, 51503, United States
Nebraska Cancer Specialists/Oncology Hematology West PC - MEJ
Council Bluffs, Iowa, 51503, United States
Iowa Methodist Medical Center
Des Moines, Iowa, 50309, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309, United States
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314, United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314, United States
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, 50263, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601, United States
Mercy Hospital South
St Louis, Missouri, 63128, United States
Community Hospital of Anaconda
Anaconda, Montana, 59711, United States
Billings Clinic Cancer Center
Billings, Montana, 59101, United States
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715, United States
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405, United States
Logan Health Medical Center
Kalispell, Montana, 59901, United States
Community Medical Center
Missoula, Montana, 59804, United States
Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
Omaha, Nebraska, 68114, United States
Nebraska Methodist Hospital
Omaha, Nebraska, 68114, United States
Oncology Associates PC
Omaha, Nebraska, 68114, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Commack
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204, United States
Novant Health Cancer Institute - Huntersville
Huntersville, North Carolina, 28078, United States
Novant Health Cancer Institute - Matthews
Matthews, North Carolina, 28105, United States
Novant Health Cancer Institute - Mooresville
Mooresville, North Carolina, 28117, United States
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501, United States
Sanford Broadway Medical Center
Fargo, North Dakota, 58122, United States
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122, United States
Good Samaritan Hospital - Cincinnati
Cincinnati, Ohio, 45220, United States
Cancer Centers of Southwest Oklahoma Research
Lawton, Oklahoma, 73505, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Oklahoma Cancer Specialists and Research Institute-Tulsa
Tulsa, Oklahoma, 74146, United States
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon, 97914, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota, 57104, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
VCU Massey Cancer Center at Stony Point
Richmond, Virginia, 23235, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
West Virginia University Healthcare
Morgantown, West Virginia, 26506, United States
Camden Clark Medical Center
Parkersburg, West Virginia, 26101, United States
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449, United States
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, 54548, United States
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, 54868, United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482, United States
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Glenn J Hanna
Alliance for Clinical Trials in Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 13, 2023
First Posted
June 15, 2023
Study Start
February 19, 2024
Primary Completion (Estimated)
June 16, 2028
Study Completion (Estimated)
June 16, 2028
Last Updated
June 12, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.