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Back|NCT05904080Recruiting
Official Title

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

Phase
Phase 2
Sponsor
National Cancer Institute (NCI)
Enrollment
50
Timeline
Feb 2024 → Jun 2028
About This Study

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 Criteria

Inclusion Criteria

  • 1Patients 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)
  • 2Recurrent, 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
  • 3Patients 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
  • 4Patients 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
  • 5Patients may have had no more than 2 prior lines of prior systemic therapy for recurrent, metastatic NPC
  • 6No prior VEGFR targeted therapy permitted
  • 7Age \>= 18 years
  • 8Eastern Cooperative Oncology Group Performance (ECOG) performance status 0-2
  • 9Absolute neutrophil count (ANC) \>= 1,000/mm\^3
  • 10Hemoglobin \>= 9 g/dL
  • 11Platelet count \>= 100,000/mm\^3
  • 12Creatinine or creatinine clearance =\< 1.5 mg/dL or \>= 30 Modification of Diet in Renal Disease (MDRD)
  • 13Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN); except subjects with Gilbert syndrome who can have a total bilirubin \< 3 mg/dL
  • 14Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGT\]) =\< 3 x upper limit of normal (ULN)
  • 15Up to =\< 5 allowed with liver metastases
  • 16Not 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.
  • 17Pregnant 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)
  • 18No active tumor bleeding: or radiographic evidence of major blood vessel infiltration as judged by the treating investigator
  • 19Prior -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.
  • 20No 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:
  • 21Repeat imaging demonstrates no new sites of bone metastases.
  • 22The lesion being considered for palliative radiation is not a target lesion
  • 23No 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
  • 24Brain 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
  • 25Human 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
  • 26For patients with evidence of chronic hepatitis B (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • 27Patients 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
  • 28Solid 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
  • 29No 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
  • 30Immune related neurologic disease,
  • 31Multiple sclerosis,
  • 32Autoimmune (demyelinating) neuropathy,
  • 33Guillain-Barre syndrome (GBS),
  • 34Myasthenia gravis;
  • 35Systemic autoimmune disease such as SLE,
  • 36Connective tissue diseases,
  • 37Scleroderma, inflammatory bowel disease (IBD),
  • 38Crohn's, ulcerative colitis,
  • 39Patients with a history of toxic epidermal necrolysis (TEN),
  • 40Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease
  • 41Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible
  • 42Patients 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
  • 43Pneumonitis should be evaluated for the nature of the disease process, need for treatment prior study treatment, and the risk of exacerbation with study treatment
  • 44Able to swallow oral medication: No known medical condition causing an inability to swallow oral formulations of agents
  • 45No 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
  • 46Concomitant 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:
  • 47Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
  • 48Therapeutic 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
  • 49Concomitant 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

91 sites participating in this study

Emory University Hospital Midtown

Atlanta, Georgia 30308

Recruiting

Nabil F. Saba

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California 92612

Recruiting

Shirin Attarian

Keck Medicine of USC Koreatown

Los Angeles, California 90020

Suspended
Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →