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

Status: Recruiting
Location: See all (91) locations...
Intervention Type: Procedure, Biological, Drug
Study Type: Interventional
Study Phase: Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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

• 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

Locations
United States
California
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
RECRUITING
Irvine
Keck Medicine of USC Koreatown
SUSPENDED
Los Angeles
Los Angeles General Medical Center
RECRUITING
Los Angeles
USC / Norris Comprehensive Cancer Center
RECRUITING
Los Angeles
USC Norris Oncology/Hematology-Newport Beach
SUSPENDED
Newport Beach
UC Irvine Health/Chao Family Comprehensive Cancer Center
RECRUITING
Orange
Stanford Cancer Institute Palo Alto
RECRUITING
Palo Alto
Georgia
Emory University Hospital Midtown
RECRUITING
Atlanta
Iowa
UI Health Care Mission Cancer and Blood - Ankeny Clinic
RECRUITING
Ankeny
Mercy Cancer Center-West Lakes
RECRUITING
Clive
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
RECRUITING
Clive
Heartland Oncology and Hematology LLP
SUSPENDED
Council Bluffs
Methodist Jennie Edmundson Hospital
RECRUITING
Council Bluffs
Nebraska Cancer Specialists/Oncology Hematology West PC - MEJ
RECRUITING
Council Bluffs
Iowa Methodist Medical Center
RECRUITING
Des Moines
Mercy Medical Center - Des Moines
RECRUITING
Des Moines
UI Health Care Mission Cancer and Blood - Des Moines Clinic
RECRUITING
Des Moines
UI Health Care Mission Cancer and Blood - Laurel Clinic
RECRUITING
Des Moines
UI Health Care Mission Cancer and Blood - Waukee Clinic
RECRUITING
Waukee
Idaho
Saint Alphonsus Cancer Care Center-Boise
SUSPENDED
Boise
Saint Alphonsus Cancer Care Center-Caldwell
SUSPENDED
Caldwell
Kootenai Health - Coeur d'Alene
RECRUITING
Coeur D'alene
Saint Alphonsus Cancer Care Center-Nampa
SUSPENDED
Nampa
Kootenai Clinic Cancer Services - Post Falls
RECRUITING
Post Falls
Kootenai Clinic Cancer Services - Sandpoint
RECRUITING
Sandpoint
Illinois
Northwestern University
RECRUITING
Chicago
University of Chicago Comprehensive Cancer Center
RECRUITING
Chicago
University of Illinois
RECRUITING
Chicago
Carle at The Riverfront
SUSPENDED
Danville
Northwestern Medicine Cancer Center Kishwaukee
RECRUITING
Dekalb
Carle Physician Group-Effingham
SUSPENDED
Effingham
NorthShore University HealthSystem-Evanston Hospital
RECRUITING
Evanston
Northwestern Medicine Cancer Center Delnor
RECRUITING
Geneva
NorthShore University HealthSystem-Glenbrook Hospital
RECRUITING
Glenview
Northwestern Medicine Glenview Outpatient Center
RECRUITING
Glenview
Northwestern Medicine Grayslake Outpatient Center
RECRUITING
Grayslake
Ingalls Memorial Hospital
RECRUITING
Harvey
NorthShore University HealthSystem-Highland Park Hospital
RECRUITING
Highland Park
Northwestern Medicine Lake Forest Hospital
RECRUITING
Lake Forest
Carle Physician Group-Mattoon/Charleston
SUSPENDED
Mattoon
UC Comprehensive Cancer Center at Silver Cross
RECRUITING
New Lenox
Northwestern Medicine Orland Park
RECRUITING
Orland Park
University of Chicago Medicine-Orland Park
RECRUITING
Orland Park
Carle Cancer Center
SUSPENDED
Urbana
Northwestern Medicine Cancer Center Warrenville
RECRUITING
Warrenville
Massachusetts
Tufts Medical Center
RECRUITING
Boston
Minnesota
Sanford Joe Lueken Cancer Center
RECRUITING
Bemidji
Missouri
Mercy Hospital South
RECRUITING
St Louis
Montana
Community Hospital of Anaconda
RECRUITING
Anaconda
Billings Clinic Cancer Center
RECRUITING
Billings
Bozeman Health Deaconess Hospital
RECRUITING
Bozeman
Benefis Sletten Cancer Institute
RECRUITING
Great Falls
Logan Health Medical Center
RECRUITING
Kalispell
Community Medical Center
RECRUITING
Missoula
North Carolina
UNC Lineberger Comprehensive Cancer Center
RECRUITING
Chapel Hill
Novant Health Presbyterian Medical Center
RECRUITING
Charlotte
Novant Health Cancer Institute - Huntersville
RECRUITING
Huntersville
Novant Health Cancer Institute - Matthews
RECRUITING
Matthews
Novant Health Cancer Institute - Mooresville
RECRUITING
Mooresville
North Dakota
Sanford Bismarck Medical Center
RECRUITING
Bismarck
Sanford Broadway Medical Center
RECRUITING
Fargo
Sanford Roger Maris Cancer Center
RECRUITING
Fargo
Nebraska
Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
RECRUITING
Omaha
Nebraska Methodist Hospital
RECRUITING
Omaha
Oncology Associates PC
SUSPENDED
Omaha
New Jersey
Memorial Sloan Kettering Basking Ridge
RECRUITING
Basking Ridge
Memorial Sloan Kettering Monmouth
RECRUITING
Middletown
Memorial Sloan Kettering Bergen
RECRUITING
Montvale
New York
Memorial Sloan Kettering Commack
RECRUITING
Commack
Memorial Sloan Kettering Westchester
RECRUITING
Harrison
Memorial Sloan Kettering Cancer Center
RECRUITING
New York
Memorial Sloan Kettering Nassau
RECRUITING
Uniondale
Ohio
Good Samaritan Hospital - Cincinnati
RECRUITING
Cincinnati
Oklahoma
Cancer Centers of Southwest Oklahoma Research
RECRUITING
Lawton
University of Oklahoma Health Sciences Center
RECRUITING
Oklahoma City
Oklahoma Cancer Specialists and Research Institute-Tulsa
SUSPENDED
Tulsa
Oregon
Saint Alphonsus Cancer Care Center-Ontario
SUSPENDED
Ontario
Oregon Health and Science University
RECRUITING
Portland
South Carolina
Medical University of South Carolina
RECRUITING
Charleston
South Dakota
Sanford Cancer Center Oncology Clinic
RECRUITING
Sioux Falls
Sanford USD Medical Center - Sioux Falls
RECRUITING
Sioux Falls
Tennessee
Vanderbilt University/Ingram Cancer Center
RECRUITING
Nashville
Virginia
VCU Massey Comprehensive Cancer Center
RECRUITING
Richmond
Wisconsin
Marshfield Medical Center-EC Cancer Center
RECRUITING
Eau Claire
Marshfield Medical Center-Marshfield
RECRUITING
Marshfield
Marshfield Medical Center - Minocqua
RECRUITING
Minocqua
Marshfield Medical Center-Rice Lake
RECRUITING
Rice Lake
Marshfield Medical Center-River Region at Stevens Point
RECRUITING
Stevens Point
Marshfield Medical Center - Weston
RECRUITING
Weston
West Virginia
West Virginia University Healthcare
RECRUITING
Morgantown
Camden Clark Medical Center
RECRUITING
Parkersburg
Time Frame
Start Date: 2024-02-19
Estimated Completion Date: 2028-06-16
Participants
Target number of participants: 50
Treatments
Active_comparator: 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.
Experimental: 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.
Related Therapeutic Areas
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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