Testing Nivolumab and Ipilimumab Immunotherapy With or Without the Targeted Drug Cabozantinib in Recurrent, Metastatic, or Incurable Nasopharyngeal Cancer

Paused · Phase 2

Conditions studied: Metastatic Nasopharyngeal Carcinoma, Recurrent Nasopharyngeal Carcinoma, Stage IV Nasopharyngeal Carcinoma AJCC v8

In brief

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.

Key facts

Study ID

NCT05904080

Run by

National Cancer Institute (NCI)

People needed

50

Starts

2024-02-19

Expected to finish

2028-06-16

Last updated by the study team

2026-06-15

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
• Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test, per institution standard, done =< 7 days prior to registration is required.
• Pregnant women are excluded from this study because nivolumab, ipilimumab, and cabozantinib are all Class C or D agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants, secondary to treatment of the mother with any of the study agents, breastfeeding should be discontinued if the mother is treated with as part of this study (in either arm)
• No active tumor bleeding: or radiographic evidence of major blood vessel infiltration as judged by the treating investigator
• Prior -anti-cancer therapy is allowed: Patients need to be recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1), with the exception of alopecia. Any life-threatening events clearly attributable to prior immunotherapy exposure that have a high possibility of recurring should warrant exclusion: including severe pneumonitis, grade 4 bullous dermatitis/drug reaction with eosinophilia and systemic symptoms (DRESS), neurologic events such as autoimmune encephalitis transverse myelitis, and/or myocarditis. Maintenance hormonal replacement or long-term hormonal therapy exposure is permitted.
• 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

Where it is running

• Iowa Methodist Medical Center — Des Moines, Iowa, United States
• UI Health Care Mission Cancer and Blood - Des Moines Clinic — Des Moines, Iowa, United States
• UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care — Irvine, California, United States
• Keck Medicine of USC Koreatown — Los Angeles, California, United States
• Los Angeles General Medical Center — Los Angeles, California, United States
• USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States
• USC Norris Oncology/Hematology-Newport Beach — Newport Beach, California, United States
• UC Irvine Health/Chao Family Comprehensive Cancer Center — Orange, California, United States
• Stanford Cancer Institute Palo Alto — Palo Alto, California, United States
• Emory University Hospital Midtown — Atlanta, Georgia, United States
• Saint Alphonsus Cancer Care Center-Boise — Boise, Idaho, United States
• Saint Alphonsus Cancer Care Center-Caldwell — Caldwell, Idaho, United States
• Kootenai Health - Coeur d'Alene — Coeur d'Alene, Idaho, United States
• Saint Alphonsus Cancer Care Center-Nampa — Nampa, Idaho, United States
• Kootenai Clinic Cancer Services - Post Falls — Post Falls, Idaho, United States
• Kootenai Clinic Cancer Services - Sandpoint — Sandpoint, Idaho, United States
• Northwestern University — Chicago, Illinois, United States
• University of Illinois — Chicago, Illinois, United States
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States
• Carle at The Riverfront — Danville, Illinois, United States
• Northwestern Medicine Cancer Center Kishwaukee — DeKalb, Illinois, United States
• Carle Physician Group-Effingham — Effingham, Illinois, United States
• NorthShore University HealthSystem-Evanston Hospital — Evanston, Illinois, United States
• Northwestern Medicine Cancer Center Delnor — Geneva, Illinois, United States
• Nebraska Cancer Specialists/Oncology Hematology West PC - MEJ — Council Bluffs, Iowa, United States

Full record on ClinicalTrials.gov

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