Testing Nivolumab and Ipilimumab Immunotherapy With or Without the Targeted Drug Cabozantinib in Recurrent, Metastatic, or Incurable Nasopharyngeal Cancer
NCT ID: NCT05904080
Last Updated: 2025-11-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
50 participants
INTERVENTIONAL
2024-02-19
2028-06-16
Brief Summary
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Detailed Description
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I. To determine if the progression-free survival (PFS) of the triplet combination (cabozantinib S-malate, nivolumab, and ipilimumab \[CaboNivoIpi\]) is more favorable than the doublet (nivolumab and ipilimumab \[NivoIpi\]).
SECONDARY OBJECTIVES:
I. To compare safety and tolerability between the two arms (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]5.0.).
II. To compare overall response rate (ORR) between the two arms via both Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune-modified Response Evaluation Criteria in Solid Tumors (iRECIST) criteria.
III. To compare overall survival (OS) between the two arms. IV. To assess response by primary or acquired PD-1/L1 inhibitor resistance in the prior line of therapy.
EXPLORATORY OBJECTIVE:
I. To evaluate molecular and immunologic predictors of response (Epstein-Barr virus \[EBV\] viral load; PD-L1 score) between arms.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive nivolumab intravenously (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 computed tomography (CT) or magnetic resonance imaging (MRI) and collection of blood samples throughout the trial.
ARM B: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 and cabozantinib S-malate orally (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.
After completion of study treatment, patients are followed up every 8-12 weeks until progression of disease occurs or a new non-protocol anti-cancer therapy is initiated and then every 6 months for up to 2 years.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm A (nivolumab, ipilimumab)
Patients 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.
Biospecimen Collection
Undergo collection of blood samples
Computed Tomography
Undergo CT scan
Ipilimumab
Given IV
Magnetic Resonance Imaging
Undergo MRI
Nivolumab
Given IV
Arm B (nivolumab, ipilimumab, cabozantinib)
Patients 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.
Biospecimen Collection
Undergo collection of blood samples
Cabozantinib S-malate
Given PO
Computed Tomography
Undergo CT scan
Ipilimumab
Given IV
Magnetic Resonance Imaging
Undergo MRI
Nivolumab
Given IV
Interventions
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Biospecimen Collection
Undergo collection of blood samples
Cabozantinib S-malate
Given PO
Computed Tomography
Undergo CT scan
Ipilimumab
Given IV
Magnetic Resonance Imaging
Undergo MRI
Nivolumab
Given IV
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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;
* Systemic autoimmune disease such as SLE,
* Connective tissue diseases,
* Scleroderma, inflammatory bowel disease (IBD),
* Crohn's, ulcerative colitis,
* Patients with a history of toxic epidermal necrolysis (TEN),
* Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease
* Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible
* Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome, and psoriasis controlled with topical medication and patients with only positive serology, such as antinuclear antibodies (ANA) or anti-thyroid antibodies, should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
* Pneumonitis should be evaluated for the nature of the disease process, need for treatment prior study treatment, and the risk of exacerbation with study treatment
* Able to swallow oral medication: No known medical condition causing an inability to swallow oral formulations of agents
* No condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study registration. Patients are permitted the use of topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Adrenal replacement steroid doses \> 10 mg daily prednisone are permitted. A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by a contact allergen) is permitted
* Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel) is prohibited. Allowed anticoagulants are the following:
* Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
* Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
* Concomitant use of any medications or substances that are strong inhibitors or inducers of CYP3A4 is discouraged; if unavoidable, the dose of cabozantinib on study should be adjusted accordingly. Any complementary medications (e.g., herbal supplements or traditional Chinese medicines) intended to treat the disease under study are prohibited
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Glenn J Hanna
Role: PRINCIPAL_INVESTIGATOR
Alliance for Clinical Trials in Oncology
Locations
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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
NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois, United States
Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois, United States
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois, United States
Ingalls Memorial Hospital
Harvey, Illinois, United States
NorthShore University HealthSystem-Highland Park Hospital
Highland Park, Illinois, United States
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, United States
Northwestern Medicine Orland Park
Orland Park, Illinois, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, United States
Carle Cancer Center
Urbana, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, United States
Mercy Cancer Center-West Lakes
Clive, Iowa, United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, United States
Heartland Oncology and Hematology LLP
Council Bluffs, Iowa, United States
Methodist Jennie Edmundson Hospital
Council Bluffs, Iowa, United States
Nebraska Cancer Specialists/Oncology Hematology West PC - MEJ
Council Bluffs, Iowa, United States
Iowa Methodist Medical Center
Des Moines, Iowa, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
Des Moines, Iowa, United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, United States
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, United States
Tufts Medical Center
Boston, Massachusetts, United States
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, United States
Mercy Hospital South
St Louis, Missouri, United States
Community Hospital of Anaconda
Anaconda, Montana, United States
Billings Clinic Cancer Center
Billings, Montana, United States
Bozeman Health Deaconess Hospital
Bozeman, Montana, United States
Benefis Sletten Cancer Institute
Great Falls, Montana, United States
Logan Health Medical Center
Kalispell, Montana, United States
Community Medical Center
Missoula, Montana, United States
Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
Omaha, Nebraska, United States
Nebraska Methodist Hospital
Omaha, Nebraska, United States
Oncology Associates PC
Omaha, Nebraska, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, United States
Memorial Sloan Kettering Commack
Commack, New York, United States
Memorial Sloan Kettering Westchester
Harrison, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, United States
Novant Health Cancer Institute - Huntersville
Huntersville, North Carolina, United States
Novant Health Cancer Institute - Matthews
Matthews, North Carolina, United States
Novant Health Cancer Institute - Mooresville
Mooresville, North Carolina, United States
Sanford Bismarck Medical Center
Bismarck, North Dakota, United States
Sanford Broadway Medical Center
Fargo, North Dakota, United States
Sanford Roger Maris Cancer Center
Fargo, North Dakota, United States
Good Samaritan Hospital - Cincinnati
Cincinnati, Ohio, United States
Cancer Centers of Southwest Oklahoma Research
Lawton, Oklahoma, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Oklahoma Cancer Specialists and Research Institute-Tulsa
Tulsa, Oklahoma, United States
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon, United States
Oregon Health and Science University
Portland, Oregon, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
West Virginia University Healthcare
Morgantown, West Virginia, United States
Camden Clark Medical Center
Parkersburg, West Virginia, United States
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, United States
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, United States
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, United States
Marshfield Medical Center - Weston
Weston, Wisconsin, United States
Countries
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Facility Contacts
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Other Identifiers
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NCI-2023-04469
Identifier Type: REGISTRY
Identifier Source: secondary_id
A092105
Identifier Type: OTHER
Identifier Source: secondary_id
A092105
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2023-04469
Identifier Type: -
Identifier Source: org_study_id
NCT06010095
Identifier Type: -
Identifier Source: nct_alias