Language: BG BG
← Back to results
Recruiting Phase 2 NCT05904080

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

Phase 2 – studying effectiveness and dosage
Conditions: Metastatic Nasopharyngeal Carcinoma Recurrent Nasopharyngeal Carcinoma Stage IV Nasopharyngeal Carcinoma AJCC v8

Sponsor: National Cancer Institute (NCI)

trial.available_in: БГ
Overview
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.
Description
PRIMARY OBJECTIVE: 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.
Who can participate
Inclusion Criteria: * 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
Interventions
Biospecimen Collection
PROCEDURE
Cabozantinib S-malate
DRUG
Computed Tomography
PROCEDURE
Ipilimumab
BIOLOGICAL
Magnetic Resonance Imaging
PROCEDURE
Nivolumab
BIOLOGICAL
Locations 92
United States (92)
Community Hospital of Anaconda
Anaconda , Montana
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny , Iowa
Site Public Contact
Emory University Hospital Midtown
Atlanta , Georgia
Site Public Contact
Memorial Sloan Kettering Basking Ridge
Basking Ridge , New Jersey
Site Public Contact
Sanford Joe Lueken Cancer Center
Bemidji , Minnesota
Billings Clinic Cancer Center
Billings , Montana
Sanford Bismarck Medical Center
Bismarck , North Dakota
Saint Alphonsus Cancer Care Center-Boise
Boise , Idaho
SUSPENDED
Tufts Medical Center
Boston , Massachusetts
Bozeman Health Deaconess Hospital
Bozeman , Montana
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell , Idaho
SUSPENDED
UNC Lineberger Comprehensive Cancer Center
Chapel Hill , North Carolina
Medical University of South Carolina
Charleston , South Carolina
Novant Health Presbyterian Medical Center
Charlotte , North Carolina
Northwestern University
Chicago , Illinois
University of Illinois
Chicago , Illinois
Site Public Contact
University of Chicago Comprehensive Cancer Center
Chicago , Illinois
Good Samaritan Hospital - Cincinnati
Cincinnati , Ohio
Mercy Cancer Center-West Lakes
Clive , Iowa
Site Public Contact
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive , Iowa
Site Public Contact
Kootenai Health - Coeur d'Alene
Coeur d'Alene , Idaho
Memorial Sloan Kettering Commack
Commack , New York
Site Public Contact
Heartland Oncology and Hematology LLP
Council Bluffs , Iowa
SUSPENDED
Methodist Jennie Edmundson Hospital
Council Bluffs , Iowa
Nebraska Cancer Specialists/Oncology Hematology West PC - MEJ
Council Bluffs , Iowa
SUSPENDED
Carle at The Riverfront
Danville , Illinois
Northwestern Medicine Cancer Center Kishwaukee
DeKalb , Illinois
Iowa Methodist Medical Center
Des Moines , Iowa
Site Public Contact
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines , Iowa
Site Public Contact
Mercy Medical Center - Des Moines
Des Moines , Iowa
Site Public Contact
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines , Iowa
Site Public Contact
Marshfield Medical Center-EC Cancer Center
Eau Claire , Wisconsin
Carle Physician Group-Effingham
Effingham , Illinois
NorthShore University HealthSystem-Evanston Hospital
Evanston , Illinois
Site Public Contact
Sanford Broadway Medical Center
Fargo , North Dakota
Sanford Roger Maris Cancer Center
Fargo , North Dakota
Northwestern Medicine Cancer Center Delnor
Geneva , Illinois
NorthShore University HealthSystem-Glenbrook Hospital
Glenview , Illinois
Site Public Contact
Northwestern Medicine Glenview Outpatient Center
Glenview , Illinois
Site Public Contact
Northwestern Medicine Grayslake Outpatient Center
Grayslake , Illinois
Site Public Contact
Benefis Sletten Cancer Institute
Great Falls , Montana
Memorial Sloan Kettering Westchester
Harrison , New York
Site Public Contact
Ingalls Memorial Hospital
Harvey , Illinois
NorthShore University HealthSystem-Highland Park Hospital
Highland Park , Illinois
Site Public Contact
Novant Health Cancer Institute - Huntersville
Huntersville , North Carolina
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine , California
Logan Health Medical Center
Kalispell , Montana
Northwestern Medicine Lake Forest Hospital
Lake Forest , Illinois
Cancer Centers of Southwest Oklahoma Research
Lawton , Oklahoma
Site Public Contact
Keck Medicine of USC Koreatown
Los Angeles , California
SUSPENDED
Los Angeles General Medical Center
Los Angeles , California
USC / Norris Comprehensive Cancer Center
Los Angeles , California
Site Public Contact
Marshfield Medical Center-Marshfield
Marshfield , Wisconsin
Novant Health Cancer Institute - Matthews
Matthews , North Carolina
Carle Physician Group-Mattoon/Charleston
Mattoon , Illinois
Memorial Sloan Kettering Monmouth
Middletown , New Jersey
Site Public Contact
Marshfield Medical Center - Minocqua
Minocqua , Wisconsin
Community Medical Center
Missoula , Montana
Memorial Sloan Kettering Bergen
Montvale , New Jersey
Site Public Contact
Novant Health Cancer Institute - Mooresville
Mooresville , North Carolina
West Virginia University Healthcare
Morgantown , West Virginia
Saint Alphonsus Cancer Care Center-Nampa
Nampa , Idaho
SUSPENDED
Vanderbilt University/Ingram Cancer Center
Nashville , Tennessee
SUSPENDED
UC Comprehensive Cancer Center at Silver Cross
New Lenox , Illinois
Memorial Sloan Kettering Cancer Center
New York , New York
Site Public Contact
USC Norris Oncology/Hematology-Newport Beach
Newport Beach , California
Site Public Contact
University of Oklahoma Health Sciences Center
Oklahoma City , Oklahoma
Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
Omaha , Nebraska
Site Public Contact
Nebraska Methodist Hospital
Omaha , Nebraska
Site Public Contact
Oncology Associates PC
Omaha , Nebraska
SUSPENDED
Saint Alphonsus Cancer Care Center-Ontario
Ontario , Oregon
SUSPENDED
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange , California
Northwestern Medicine Orland Park
Orland Park , Illinois
University of Chicago Medicine-Orland Park
Orland Park , Illinois
Stanford Cancer Institute Palo Alto
Palo Alto , California
Camden Clark Medical Center
Parkersburg , West Virginia
Oregon Health and Science University
Portland , Oregon
Kootenai Clinic Cancer Services - Post Falls
Post Falls , Idaho
Marshfield Medical Center-Rice Lake
Rice Lake , Wisconsin
VCU Massey Cancer Center at Stony Point
Richmond , Virginia
Site Public Contact
VCU Massey Comprehensive Cancer Center
Richmond , Virginia
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint , Idaho
Sanford Cancer Center Oncology Clinic
Sioux Falls , South Dakota
Sanford USD Medical Center - Sioux Falls
Sioux Falls , South Dakota
Mercy Hospital South
St Louis , Missouri
Marshfield Medical Center-River Region at Stevens Point
Stevens Point , Wisconsin
Oklahoma Cancer Specialists and Research Institute-Tulsa
Tulsa , Oklahoma
SUSPENDED
Memorial Sloan Kettering Nassau
Uniondale , New York
Site Public Contact
Carle Cancer Center
Urbana , Illinois
Northwestern Medicine Cancer Center Warrenville
Warrenville , Illinois
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee , Iowa
Site Public Contact
Marshfield Medical Center - Weston
Weston , Wisconsin
Technical details
Status
Recruiting
Phase
Phase 2
Study type
INTERVENTIONAL
Sex
Male and female
Minimum age
18 Years
Healthy volunteers
No
Start date
19.02.2024
Completion date
16.06.2028
Registry ID
NCT05904080
Source
clinicaltrials.gov
trial.inquiry_btn

Information is automatically extracted from ClinicalTrials.gov. Consult your doctor before taking action.