A RANDOMIZED PHASE II STUDY OF NIVOLUMAB VERSUS NIVOLUMAB AND BMS-986016 (RELATLIMAB) AS MAINTENANCE TREATMENT AFTER FIRST-LINE TREATMENT WITH PLATINUM-GEMCITABINE-NIVOLUMAB FOR PATIENTS WITH EPSTEIN-BARR VIRUS-ASSOCIATED RECURRENT/METASTATIC NASOPHARYNGEAL CARCINOMA

Not Applicable

• Conditions: Neoplasms

• Registration Number: KCT0009487
• Lead Sponsor: Seoul National University Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 24 June 2024

Recruitment & Eligibility

• Status: ot yet recruiting
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

1. Pathologically (histologically or cytologically) proven diagnosis of nasopharyngeal carcinoma (NPC) that has recurred locoregionally and/or is present at distant sites. Patients who present with metastatic disease (de novo) at diagnosis are also eligible. For locoregional recurrence, the disease must not be amenable to potentially curative surgery or re-irradiation.
•Tumor showing (histological/cytological) EBER-positivity
•A known history of detectable plasma EBV DNA (via a PCR-based assay) at any time point since the initial diagnosis of NPC.

2. Measurable disease as defined by RECIST 1.1 criteria. Lesion(s) that have been irradiated previously can be counted as measurable as long as radiological progression after the prior radiation therapy has been demonstrated.
•Contrast enhanced CT scan of the chest. The contrast enhanced CT component of a whole-body PET-CT is also acceptable. The plain (non-contrast) CT component of a PET-CT is not acceptable.
•CT the abdomen and pelvis, if clinically indicated (diagnostic quality with contrast, unless contraindicated).
•Patients with known locoregional disease must have contrast enhanced MRI or CT of the nasopharynx and neck as this disease site(s) may be assessed as target lesions. For patients without known locoregional disease, imaging of the nasopharynx and neck is optional.
•Symptomatic and active brain metastases and/or leptomeningeal metastasis on CT and/or MRI imaging: Patients who have prior therapies for brain and leptomeningeal metastasis or cord/cauda compression who are clinically stable for = 2 months prior to registration and have discontinued systemic steroids therapy (> 10 mg/day prednisone or equivalent) > 4 weeks prior to registration are eligible.
•Patients with base of skull involvement by NPC are allowed unless their disease is directly invading the brain parenchyma, associated with clinical symptoms and/or significant vasogenic edema on radiological imaging.

3. Aged 19 years or older

4. ECOG PS 0-2

5. Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal.

6. Adequate Organ Function Laboratory Values
•Hematological
Absolute neutrophil count (ANC) = 1500 cells/mm3
Platelets= 100,000 cells/mm3
Hemoglobin (Hgb) = 8.0 g/dL (Transfusion is accepted. Erythropoietin dependency not accepted.)
•Hepatic
Total bilirubin = 1.5 × institutional upper limit of normal (ULN) OR direct bilirubin = ULN for patients with total bilirubin levels > 1.5 × ULN. Patients with known Gilbert’s disease who have serum bilirubin level = 3 × ULN may be enrolled.
ALT (SGPT) = 3 × ULN (= 5 × ULN for patients with liver metastases)
•Renal
Serum creatinine OR Calculated creatinine clearance (CrCl) based on Cockcroft-Gault equation = 1.5× ULN
OR > 30 mL/min for patients with serum creatinine levels > 1.5 × ULN. Cisplatin or carboplatin may be used at the discretion of the investigator – except for patients with CrCl between 30-50 mL/min, for whom carboplatin should be used instead of cisplatin. CrCl must be > 50 mL/min for cisplatin to be used.
Albumin-Adjusted calcium level based on corrected calcium equation= 1.5× ULN (patients are allowed to have treatment for hypercalcemia prior to starting treatment).

Exclusion Criteria

1. If the subject does not have an appropriate health status conducive to compliance with the clinical trial plan and feasible follow-up.
2. If the subject is HIV, HBV, and/or HCV co-infected.
•HIV-infected subjects who have received effective antiretroviral therapy with undetectable virus levels within the past 6 months may be eligible, provided that the trial site has experience with HIV subjects receiving anticancer chemotherapy and immunotherapy and can provide appropriate medical management.
•If evidence of chronic hepatitis B virus (HBV) infection, except when plasma HBV DNA is undetectable during antiviral therapy.
•If history of hepatitis C virus (HCV) infection, except for those who have been treated and cured. For those currently under treatment for HCV infection, registration is only allowed if the HCV virus (HCV-RNA negative) is not detected.
3. If the subject cannot provide a blood sample for plasma EBV DNA purposes as specified in the study protocol at the time indicated.
4. If the subject has or had a malignancy that could interfere with the safety or efficacy evaluation of the investigational therapy.
5. If there is a possibility of pregnancy (fertile women or male subjects who can impregnate a woman), unless the subject intends to use effective contraception for up to 5 months during and after completion of the investigational treatment, as agreed upon by the principal investigator based on the advice of the attending physician (definition of effective contraception is provided in Protocol Section 9).
6. Subjects with prior treatment:
•No systemic treatment for R/M NPC, including salvage systemic therapy, is allowed. Treatment for non-recurrent and non-metastatic NPC is permitted.
•Treatment with PD-1 inhibitors (except for adjuvant or neoadjuvant therapy for NPC), PD-L1 inhibitors, anti-PD-L2 inhibitors, LAG-3 inhibitors, CTLA-4 inhibitors (except for adjuvant or neoadjuvant therapy for non-recurrent and non-metastatic NPC), T-cell co-stimulation, or other antibodies or drugs targeting immune checkpoint pathways is not allowed.
•If the time interval between the last treatment for curative intent therapy and the recurrence is 6 months or more for non-recurrent and non-metastatic NPC, including radical radiotherapy (RT) and/or induction, concurrent, or adjuvant chemotherapy.
•Toxicities from previous systemic or radiation therapy must have recovered to NCI CTCAE v5.0 grade 0 or 1 (except for alopecia, dry mouth, dysgeusia, dysphagia, and fatigue) before registration. Subjects who experienced cisplatin-related neuropathy must have recovered to grade 0-2 before registration. Subjects who experienced hearing impairment or ototoxicity after cisplatin treatment may register at any grade according to NCI CTCAE v5.0 criteria.
•Palliative radiotherapy within 30 days before registration is not allowed. This includes palliative RT to recurrent/metastatic sites. The irradiated area should not be the sole measurable lesion of recurrent disease.
•Major surgical procedures within 30 days before registration are not allowed.
7. Excluded for subjects with concurrent conditions:
•History of unstable angina requiring hospitalization within the past 6 months.
•History of myocardial infarction within the past 6 months.
•NYHA functional classification III/IV.
•History of myocarditis.
•Active infection requiring intravenous antibiotic, antiviral, or antifungal therapy at the time of enrollment.
•Steroid-req

Study & Design

• Study Type: Interventional Study
• Study Design: Not specified