Metastatic Nasopharyngeal CarcinomaPhase 2NCT06029270
Testing the Addition of BMS-986016 (Relatlimab) to the Usual Immunotherapy After Initial Treatment for Recurrent or Metastatic Nasopharyngeal Cancer
A Phase 2 study testing Biospecimen Collection, Bone Scan and Carboplatin in people with Metastatic Nasopharyngeal Carcinoma and Recurrent Nasopharyngeal Carcinoma, run by National Cancer Institute (NCI) at 95 sites in 5 countries.
Trial summary
This phase II trial tests the addition of BMS-986016 (relatlimab) to the usual immunotherapy after initial treatment for nasopharyngeal cancer that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Nasopharyngeal Carcinoma, Recurrent Nasopharyngeal Carcinoma, Stage IV Nasopharyngeal Carcinoma AJCC v8
- What is being tested?
- Biospecimen Collection, Bone Scan and Carboplatin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 156 participants
- Where
- 95 sitesin 5 countries
- Study dates
- 15 Jul 2024to 30 Apr 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PRIOR TO STEP 1 REGISTRATION:
- 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. Eligible patient must have the following characteristics:
- Tumor showing (histological/cytological) Epstein-Barr encoded ribonucleic acid (EBER)-positivity (e.g., In situ hybridization, immunohistochemistry) or
- A known history of detectable plasma EBV DNA (via a polymerase chain reaction [PCR]-based assay) at any time point since the initial diagnosis of NPC.
- 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.
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- 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.
- Age >= 18 years.
- Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status of 0-2.
- 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.
- Absolute neutrophil count (ANC) >= 1500 cells/mm^3.
- Platelets >= 100,000 cells/mm^3.
- Hemoglobin (Hgb) >= 8.0 g/dL (Transfusion is accepted. Erythropoietin dependency not accepted.).
- 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.
- Alanine transaminase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 × ULN (=< 5 × ULN for patients with liver metastases).
- Serum creatinine =< 1.5 × ULN or calculated creatinine clearance (CrCl) based on Cockcroft-Gault equation >= 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).
- No prior systemic treatment of palliative intent for recurrent/metastatic (R/M) NPC including cytotoxic chemotherapy. Prior treatment for non-recurrent and non-metastatic NPC is allowed. Systemic therapy given prior to curative intent re-irradiation or surgery is allowed for potentially curable locoregional recurrence.
- No prior treatment with a PD-1 inhibitor (except if given as adjuvant or neoadjuvant therapy for NPC), PD-L1 inhibitor, anti-PD-L2 inhibitor, LAG-3 inhibitor, CTLA-4 inhibitor (except if given as adjuvant or neoadjuvant therapy for non-recurrent and non-metastatic NPC), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
- The interval between the last dose of curative-intent treatment for non-recurrent, non-metastatic NPC, including definitive radiotherapy (RT) and/or induction, concurrent, or adjuvant chemotherapy and recurrence must be ˃ 6 months.
- Clinically significant toxicities from any prior systemic therapy or radiotherapy must have resolved to grade 0 or 1 as per National Cancer Institute (NCI) CTCAE v 5.0 - except alopecia, dry mouth, dysgeusia, dysphagia, and fatigue. Patients with a history of grade 3-4 cisplatin related neuropathy must have recovered to grade 0-2 prior to registration. Patients with a history of hearing impairment, or ototoxicity from prior cisplatin, of any grade are allowed.
- No prior palliative RT within 30 days prior to registration unless the irradiated site(s) are not the target lesions. The irradiated site(s) also must not be the only sites of measurable recurrent disease.
- No major surgical procedures within 30 days prior to registration.
- No history of unstable angina requiring hospitalization within the last 6 months.
- No history of myocardial infarction within the last 6 months.
- New York Heart Association Functional Classification II or better (New York Heart Association [NYHA] Functional Classification III/IV are not eligible). Patients with symptomatic coronary artery disease, congestive heart failure or a known history of having a left ventricular ejection fraction < 50% must be stably controlled with medication in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
- No prior history of myocarditis.
- No active infection requiring IV antibiotics, IV antiviral, or IV antifungal treatments at the time of study registration.
- No history of (non-infectious) pneumonitis that required steroids or current pneumonitis requiring steroids and/or immunosuppressive therapy, idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans), or idiopathic pneumonitis.
- No history of multi-drug resistant mycobacterium tuberculosis (TB) or active TB, as defined by systemic treatment received =< 2 years prior to registration. Note: Patients who had a history of treated TB ˃ 2 years prior to registration are allowed.
- No prior solid organ transplant or bone marrow transplant.
- No conditions requiring systemic treatment with either immunosuppressive doses of corticosteroids (> 10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Steroid premedication for the prophylaxis of CT contrast-related allergies is allowed. The use of dexamethasone as an anti-emetic premedication prior to chemotherapy is also allowed.
- No active autoimmune disease requiring systemic treatment (i.e., disease modifying agents, corticosteroids, or immunosuppressive drugs) within the past 2 years. These may include (but not limited to) patients with a history of immune-related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), rheumatoid arthritis, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, autoimmune hepatitis, glomerulonephritis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome.
- Note: Patients are permitted to enroll if they have vitiligo; type I diabetes mellitus; hypothyroidism, pituitary or adrenal insufficiency requiring only hormone replacement; alopecia; and/or psoriasis not requiring systemic treatment. Conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- No prior live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist [registered trademark]) are live attenuated vaccines and are not allowed. Coronavirus disease 2019 (COVID-19) vaccines that are approved by the local drug regulatory authority of the participating region are allowed.
- No known history of grade 3-4 allergic reaction or hypersensitivity reaction to cisplatin, carboplatin, or gemcitabine.
- No known history of grade 4 hypersensitivity (or infusion) reaction to any monoclonal antibody. Patients who had prior grade 3 hypersensitivity (or infusion) reaction but could tolerate resumption of the antibody treatment after appropriate pre-medication are eligible.
- PRIOR TO STEP 2 REGISTRATION:
- Collection of plasma EBV DNA at baseline is mandatory for all patients prior to Step 2 registration and induction treatment.
- Note: Submission of the baseline sample will be batch shipped.
- PRIOR TO STEP 3 REGISTRATION/RANDOMIZATION: PATIENTS WITHOUT PROGRESSIVE DISEASE (PD) ONLY:
- All patients must have received minimum of 3 cycles, and up to a maximum of 6 cycles of induction treatment within 20 weeks from cycle 1, day 1 of induction treatment (i.e., patients must have completed all induction treatment within 20 weeks from cycle 1 day 1, including the treatment breaks). Patients must have completed 6 cycles of induction treatment, except in the following circumstances:
- Significant dose delays as a result of treatment-related toxicities.
- Intercurrent illness(s), that rendered the patient unable to continue induction treatment.
- Note: If a patient received < 6 cycles of induction treatment for reasons other than the above circumstances, they will not be eligible for randomization.
- A CT scan within 30 days prior to Step 3 registration/randomization is required. If the most recent scan performed is not within this time frame, a repeat scan is required to assess response.
- Did not meet any criteria that result in permanent discontinuation of study treatment during induction treatment phase.
- Must meet the criteria for starting/resuming a new cycle of maintenance treatment.
- Did not experience any nivolumab-related autoimmune toxicities that would result in permanent discontinuation of nivolumab during the induction treatment phase.
- Collection of the plasma EBV DNA post-induction treatment is mandatory.
- Note: Submission of the post-induction sample will be batch shipped.
Who cannot join
None listed.
Trial locations and contacts
95 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
95 sites in 5 countries
United States90 sites, 78 recruiting
- Recruiting
Community Hospital of Anaconda
Anaconda, Montana, 59711
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Recruiting
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023
Site Public Contact, 515-241-3305
Seema Harichand-Herdt
- Recruiting
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Site Public Contact, 888-946-7447
Conor E. Steuer
- Recruiting
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
Site Public Contact, 212-639-7592
Alan L. Ho
- Recruiting
Billings Clinic Cancer Center
Billings, Montana, 59101
Site Public Contact, 800-996-2663, research@billingsclinic.org
John M. Schallenkamp
- Suspended
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
- Recruiting
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Suspended
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605
- Recruiting
Saint Anthony Regional Hospital
Carroll, Iowa, 51401
Site Public Contact, 515-689-7658, sbenson@iora.org
Seema Harichand-Herdt
- Recruiting
Medical University of South Carolina
Charleston, South Carolina, 29425
Site Public Contact, 843-792-9321, hcc-clinical-trials@musc.edu
John M. Kaczmar
- Recruiting
Northwestern University
Chicago, Illinois, 60611
Site Public Contact, 312-695-1301, cancer@northwestern.edu
Jochen H. Lorch
- Active, not recruiting
University of Illinois
Chicago, Illinois, 60612
- Active, not recruiting
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219
- Recruiting
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325
Site Public Contact, 515-241-3305
Seema Harichand-Herdt
- Recruiting
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Recruiting
Memorial Sloan Kettering Commack
Commack, New York, 11725
Site Public Contact, 212-639-7592
Alan L. Ho
- Suspended
Heartland Oncology and Hematology LLP
Council Bluffs, Iowa, 51503
- Suspended
Methodist Jennie Edmundson Hospital
Council Bluffs, Iowa, 51503
- Suspended
Nebraska Cancer Specialists/Oncology Hematology West PC - MEJ
Council Bluffs, Iowa, 51503
- Recruiting
Carle at The Riverfront
Danville, Illinois, 61832
Site Public Contact, 800-446-5532, Research@Carle.com
Prem Sobti
- Recruiting
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115
Site Public Contact, 630-352-5360, Donald.Smith3@nm.org
Jochen H. Lorch
- Recruiting
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
Site Public Contact, 515-241-6727
Seema Harichand-Herdt
- Recruiting
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309
Site Public Contact, 515-241-3305
Seema Harichand-Herdt
- Recruiting
Broadlawns Medical Center
Des Moines, Iowa, 50314
Site Public Contact, 515-282-2200
Seema Harichand-Herdt
- Recruiting
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314
Site Public Contact, 515-241-3305
Richard L. Deming
- Recruiting
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314
Site Public Contact, 515-241-3305
Seema Harichand-Herdt
- Recruiting
Kaiser Permanente Dublin
Dublin, California, 94568
Site Public Contact, 877-642-4691
Jed A. Katzel
- Recruiting
Carle Physician Group-Effingham
Effingham, Illinois, 62401
Site Public Contact, 800-446-5532, Research@carle.com
Prem Sobti
- Recruiting
UI Healthcare Mission Cancer and Blood - Fort Dodge
Fort Dodge, Iowa, 50501
Site Public Contact, 515-282-2921, trials@missioncancer.com
Seema Harichand-Herdt
- Recruiting
Kaiser Permanente-Fremont
Fremont, California, 94538
Site Public Contact, 877-642-4691, Kpoct@kp.org
Jed A. Katzel
- Recruiting
Kaiser Permanente Fresno Orchard Plaza
Fresno, California, 93720
Site Public Contact, 833-574-2273
Jed A. Katzel
- Recruiting
Kaiser Permanente-Fresno
Fresno, California, 93720
Site Public Contact, 877-642-4691, Kpoct@kp.org
Jed A. Katzel
- Recruiting
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134
Site Public Contact, 630-352-5360, Donald.Smith3@nm.org
Jochen H. Lorch
- Recruiting
Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois, 60026
Site Public Contact, 312-695-1102
Jochen H. Lorch
- Recruiting
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois, 60030
Site Public Contact, 312-695-1102
Jochen H. Lorch
- Recruiting
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Recruiting
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Site Public Contact, 212-639-7592
Alan L. Ho
- Recruiting
Kaiser Permanente Moanalua Medical Center
Honolulu, Hawaii, 96819
Site Public Contact, 808-432-5195, shelley.a.clark@kp.org
Jed A. Katzel
- Recruiting
Logan Health Medical Center
Kalispell, Montana, 59901
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Recruiting
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, 60045
Site Public Contact, cancertrials@northwestern.edu
Jochen H. Lorch
- Recruiting
Keck Medicine of USC Koreatown
Los Angeles, California, 90020
Site Public Contact, 213-388-0908
Jacob S. Thomas
- Recruiting
Los Angeles General Medical Center
Los Angeles, California, 90033
Site Public Contact, 323-865-0451, uscnorrisinfo@med.usc.edu
Jacob S. Thomas
- Recruiting
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Site Public Contact, 323-865-0451
Jacob S. Thomas
- Recruiting
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938
Site Public Contact, 800-446-5532, Research@carle.com
Prem Sobti
- Recruiting
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Site Public Contact, 212-639-7592
Alan L. Ho
- Recruiting
Community Medical Center
Missoula, Montana, 59804
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Recruiting
Kaiser Permanente- Modesto MOB II
Modesto, California, 95356
Site Public Contact, 877-642-4691
Jed A. Katzel
- Recruiting
Kaiser Permanente-Modesto
Modesto, California, 95356
Site Public Contact, 877-642-4691, Kpoct@kp.org
Jed A. Katzel
- Recruiting
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
Site Public Contact, 212-639-7592
Alan L. Ho
- Recruiting
ProHealth D N Greenwald Center
Mukwonago, Wisconsin, 53149
Site Public Contact, research.institute@phci.org
Timothy R. Wassenaar
- Suspended
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Site Public Contact, 212-639-7592
Alan L. Ho
- Recruiting
USC Norris Oncology/Hematology-Newport Beach
Newport Beach, California, 92663
Site Public Contact, 323-865-0451
Jacob S. Thomas
- Recruiting
Kaiser Permanente-Oakland
Oakland, California, 94611
Site Public Contact, 877-642-4691, Kpoct@kp.org
Jed A. Katzel
- Recruiting
ProHealth Oconomowoc Memorial Hospital
Oconomowoc, Wisconsin, 53066
Site Public Contact, 262-928-7878
Timothy R. Wassenaar
- Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu
Minh Phan
- Recruiting
Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
Omaha, Nebraska, 68114
Site Public Contact, 402-334-4773
Yungpo B. Su
- Recruiting
Nebraska Methodist Hospital
Omaha, Nebraska, 68114
Site Public Contact, 402-354-5144
Yungpo B. Su
- Suspended
Oncology Associates PC
Omaha, Nebraska, 68114
- Suspended
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon, 97914
- Recruiting
Northwestern Medicine Orland Park
Orland Park, Illinois, 60462
Site Public Contact, nctnprogram_rhlccc@northwestern.edu
Jochen H. Lorch
- Recruiting
Stanford Cancer Institute Palo Alto
Palo Alto, California, 94304
Site Public Contact, 650-498-7061, cancertrialsinfo@stanford.edu
Alexander D. Colevas
- Recruiting
Providence Portland Medical Center
Portland, Oregon, 97213
Site Public Contact, 503-215-2614, CanRsrchStudies@providence.org
Dan S. Zuckerman
- Recruiting
Providence Saint Vincent Medical Center
Portland, Oregon, 97225
Site Public Contact, 503-215-2614, CanRsrchStudies@providence.org
Dan S. Zuckerman
- Recruiting
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Recruiting
Kaiser Permanente-Roseville
Roseville, California, 95661
Site Public Contact, 877-642-4691, Kpoct@kp.org
Jed A. Katzel
- Recruiting
Kaiser Permanente Downtown Commons
Sacramento, California, 95814
Site Public Contact, 877-642-4691, kpoct@kp.org
Jed A. Katzel
- Recruiting
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Site Public Contact, 916-734-3089
Siao-Yi Wang
- Recruiting
Kaiser Permanente-South Sacramento
Sacramento, California, 95823
Site Public Contact, 877-642-4691, Kpoct@kp.org
Jed A. Katzel
- Recruiting
Kaiser Permanente-San Francisco
San Francisco, California, 94115
Site Public Contact, 877-642-4691, Kpoct@kp.org
Jed A. Katzel
- Recruiting
Kaiser Permanente-Santa Teresa-San Jose
San Jose, California, 95119
Site Public Contact, 877-642-4691, Kpoct@kp.org
Jed A. Katzel
- Recruiting
Kaiser Permanente San Leandro
San Leandro, California, 94577
Site Public Contact, 877-642-4691, Kpoct@kp.org
Jed A. Katzel
- Recruiting
Kaiser San Rafael-Gallinas
San Rafael, California, 94903
Site Public Contact, 877-642-4691, Kpoct@kp.org
Jed A. Katzel
- Recruiting
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, 83864
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Recruiting
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California, 95051
Site Public Contact, 877-642-4691, Kpoct@kp.org
Jed A. Katzel
- Recruiting
Kaiser Permanente-Santa Rosa
Santa Rosa, California, 95403
Site Public Contact, 877-642-4691, Kpoct@kp.org
Jed A. Katzel
- Recruiting
Swedish Medical Center-First Hill
Seattle, Washington, 98122
Site Public Contact, 206-215-2343, PCRC-NCORP@Swedish.org
Dan S. Zuckerman
- Recruiting
Kaiser Permanente-South San Francisco
South San Francisco, California, 94080
Site Public Contact, 877-642-4691, Kpoct@kp.org
Jed A. Katzel
- Recruiting
Mercy Hospital South
St Louis, Missouri, 63128
Site Public Contact, 314-525-6042, Danielle.Werle@mercy.net
Jay W. Carlson
- Recruiting
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Site Public Contact, 314-251-7066
Jay W. Carlson
- Suspended
Oklahoma Cancer Specialists and Research Institute-Tulsa
Tulsa, Oklahoma, 74146
- Recruiting
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
Site Public Contact, 212-639-7592
Alan L. Ho
- Recruiting
Carle Cancer Center
Urbana, Illinois, 61801
Site Public Contact, 800-446-5532, Research@carle.com
Prem Sobti
- Recruiting
Kaiser Permanente-Vallejo
Vallejo, California, 94589
Site Public Contact, 877-642-4691, Kpoct@kp.org
Jed A. Katzel
- Recruiting
Kaiser Permanente-Walnut Creek
Walnut Creek, California, 94596
Site Public Contact, 877-642-4691, Kpoct@kp.org
Jed A. Katzel
- Recruiting
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555
Site Public Contact, 630-352-5360, Donald.Smith3@nm.org
Jochen H. Lorch
- Recruiting
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, 50263
Site Public Contact, 515-241-3305
Seema Harichand-Herdt
- Recruiting
ProHealth Waukesha Memorial Hospital
Waukesha, Wisconsin, 53188
Site Public Contact, 262-928-7632
Timothy R. Wassenaar
- Recruiting
UW Cancer Center at ProHealth Care
Waukesha, Wisconsin, 53188
Site Public Contact, 262-928-5539, Chanda.miller@phci.org
Timothy R. Wassenaar
- Active, not recruiting
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069
Singapore2 sites, 2 recruiting
- Recruiting
National University Hospital Singapore
Singapore, 119074
Site Public Contact, horg@nuhs.edu.sg
Boon C. Goh
- Recruiting
National Cancer Centre Singapore
Singapore, 168583
Site Public Contact, 65 6225 5655, cancerhelpline@nccs.com.sg
Wan Teck D. Lim
Australia1 site, 1 recruiting
- Recruiting
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Site Public Contact, 61 3 9656 1521
Danny Rischin
Canada1 site, 1 recruiting
- Recruiting
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
Site Public Contact, 416-946-4501, clinical.trials@uhn.on.ca
Enrique Sanz Garcia
Hong Kong1 site, 1 recruiting
- Recruiting
Chinese University of Hong Kong-Prince of Wales Hospital
Shatin
Site Public Contact, ccrb@cuhk.edu.hk
Brigette B. Ma
About this study
Official title: 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 (REMAIN)
This phase II trial tests the addition of BMS-986016 (relatlimab) to the usual immunotherapy after initial treatment for nasopharyngeal cancer that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Relatlimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. The usual approach of treatment is initial treatment with chemotherapy such as the combination of cisplatin (or carboplatin) and gemcitabine, along with immunotherapy such as nivolumab. After the initial treatment is finished, patients may continue to receive additional immunotherapy. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. Giving BMS-986016 in addition to the usual immunotherapy after initial treatment may extend the time without the tumor cells growing or spreading longer than the usual approach in patients with recurrent or metastatic nasopharyngeal cancer.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine if adding BMS-986016 (relatlimab) to nivolumab maintenance therapy shows a signal of improved progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in patients who do not progress following treatment with platinum-gemcitabine-nivolumab combination in the first-line treatment of recurrent and/or metastatic nasopharyngeal carcinoma (R/M NPC).
SECONDARY OBJECTIVES:
- To determine if adding BMS-986016 (relatlimab) to nivolumab maintenance improves overall survival (OS) compared to nivolumab maintenance alone.
II. To compare patterns of failure (local-regional relapse and distant metastasis) between treatment arms.
III. To determine if adding BMS-986016 (relatlimab) to nivolumab maintenance improves objective response, duration of response, and disease control rate compared to nivolumab maintenance alone.
IV. To evaluate the tolerability of nivolumab-BMS-986016 (relatlimab) maintenance and assess and compare toxicity between arms based on the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) criteria.
- To evaluate baseline plasma Epstein-Barr virus (EBV) DNA (< 2000 copies/mL versus [vs.] >= 2000 copies/mL) as a prognostic biomarker.
VI. To validate post-induction plasma EBV DNA (detectable [>= 1 copies/mL] vs. undetectable [0 copies/mL]) as a prognostic biomarker.
EXPLORATORY OBJECTIVES:
- To collect blood and tissue specimens for future translational science studies.
II. To assess post-induction plasma EBV DNA (detectable [>= 1 copies/mL] vs. undetectable [0 copies/mL]) as a predictive biomarker.
OUTLINE:
INDUCTION THERAPY: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 of each cycle, cisplatin IV or carboplatin IV over 30-60 minutes on day 1 of each cycle and gemcitabine IV over 30 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) and blood sample collection during screening and on study.
MAINTENANCE THERAPY: Patients who do not progress radiologically are randomized to 1 of 2 arms.
ARM I: Patients receive nivolumab IV over 30 minutes. Cycles repeat every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI on study. Patients also undergo positron emission tomography (PET)/CT or bone scan as clinically indicated.
ARM II: Patients receive nivolumab IV over 30 minutes and relatlimab IV over 30-90 minutes. Cycles repeat every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI on study. Patients also undergo PET/CT or bone scan as clinically indicated.
After completion of study treatment, patients are followed up every 4 months for 2 years, every 6 months in years 3-5, and then annually.
- Conditions
- Metastatic Nasopharyngeal Carcinoma, Recurrent Nasopharyngeal Carcinoma, Stage IV Nasopharyngeal Carcinoma AJCC v8
- Being tested
- Biospecimen Collection, Bone Scan, Carboplatin, Cisplatin, Computed Tomography
- Medical subject headings
- Nasopharyngeal Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
Bone ScanProcedure or surgery
Also called Bone Scintigraphy
Undergo bone scan
CarboplatinDrug
Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino
Given IV
CisplatinDrug
Also called Abiplatin, Blastolem, Briplatin, CDDP
Given IV
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT or PET/CT
GemcitabineDrug
Also called dFdC, dFdCyd, Difluorodeoxycytidine
Given IV
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
NivolumabBiological
Also called ABP 206, BCD-263, BMS 936558, BMS-936558
Given IV
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET/CT
RelatlimabBiological
Also called BMS 986016, BMS-986016, BMS986016, Immunoglobulin G4, Anti-(human Lymphocyte Activation Gene-3 Protein) (Human Heavy Chain), Disulfide with Human Light Chain, Dimer
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I (Nivolumab) | Active comparator | Patients receive nivolumab IV over 30 minutes. Cycles repeat every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI on study. Patients also undergo PET/CT or bone scan as clinically indicated. Receives: Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Procedure: Positron Emission Tomography |
| Arm II (Nivolumab, relatlimab) | Experimental | Patients receive nivolumab IV over 30 minutes and relatlimab IV over 30-90 minutes. Cycles repeat every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI on study. Patients also undergo PET/CT or bone scan as clinically indicated. Receives: Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Procedure: Positron Emission Tomography; Biological: Relatlimab |
| Induction therapy (Platinum-gemcitabine-nivolumab) | Experimental | Patients receive nivolumab IV over 30 minutes on day 1 of each cycle, cisplatin IV or carboplatin IV over 30-60 minutes on day 1 of each cycle and gemcitabine IV over 30 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI and blood sample collection during screening and on study. Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Gemcitabine; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS)
Will be assessed in both treatment arms and will be estimated using the Kaplan-Meier method. The comparison of PFS distributions between treatment arms will be performed using the log-rank test. Additional analyses of treatment effect will be performed using Cox models with the stratification factors included as a fixed covariates, as well as other tumor and patient characteristics, listed below. Median PFS and the corresponding 95% confidence intervals (CIs) for each arm will be estimated with the Brookmeyer-Crowley method. Multivariable analysis will be performed using a Cox proportional hazards model and relevant patient and tumor characteristics (country [Asian sites versus (vs.) Non-Asian sites], keratinizing squamous carcinoma, sex, age, and baseline Epstein-Barr virus (EBV) deoxyribonucleic acid [DNA]). Hazard ratios and their respective 85% lower confidence bound, and 95% confidence intervals will be provided.
Measured: Time from randomization to progressive disease (PD) or death due to any cause, assessed up to 6 years
Secondary outcomes (8)
Overall survival (OS)
Will be estimated using the Kaplan-Meier method and between-arm differences will be assessed using the log-rank test. Median OS and the corresponding 95% CIs using log-log transformation to survival function for each arm will be estimated with the Brookmeyer-Crowley method.
Measured: Time from randomization to death due to any cause, assessed up to 6 years
Tumor response
Will be assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Cox proportional hazards models will be used to determine hazard ratios (cause-specific hazard ratios in the case of endpoints with competing risks) and to assess the effects of covariates of interest. Fine-Gray sub-distribution hazards Cox model will be used to complement the competing risk analyses.
Measured: Up to 6 years
Locoregional failure
Cox proportional hazards models will be used to determine hazard ratios (cause-specific hazard ratios in the case of endpoints with competing risks) and to assess the effects of covariates of interest. Fine-Gray sub-distribution hazards Cox model will be used to complement the competing risk analyses.
Measured: Up to 6 years
Distant metastasis
Cox proportional hazards models will be used to determine hazard ratios (cause-specific hazard ratios in the case of endpoints with competing risks) and to assess the effects of covariates of interest. Fine-Gray sub-distribution hazards Cox model will be used to complement the competing risk analyses.
Measured: Up to 6 years
Incidence of adverse events (AEs)
Will be graded using Common Terminology Criteria for Adverse Events version 5.0. Counts of all AEs by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm. The rate of patients with at least 1 grade 3 or higher AE will be compared between the treatment arms using a chi-square test for proportions and confidence intervals for rate difference will be computed using Miettinen-Nurminen (score) method
Measured: Up to 6 years
Post-induction plasma EBV DNA as a prognostic biomarker
Will be defined as a binary biomarker (detectable: >= 1 copies/mL vs. undetectable: 0 copies/mL). Biomarker effect HRs from multivariable Cox models, including key tumor and patient characteristics will also be reported.
Measured: Up to 6 years
Pre-induction plasma EBV DNA vs. progressive disease (PD) during induction treatment
Will include all patients treated with concurrent (induction) treatment and a binary biomarker based on pre-induction plasma EBV DNA (< 2000 vs. ≥2000 copies/mL). PD rates during induction for each biomarker subgroup will be computed assuming a binomial distribution and compared between biomarker subgroups using a chi-square test. Multivariable Cox models, including key tumor and patient characteristics will also be included.
Measured: Up to 6 years
Persistent plasma EBV DNA vs. PFS
Will examine the association between persistent EBV DNA after induction treatment and PFS. Only randomized patients with positive pre-induction plasma EBV DNA will be included (~90-95%). Patients will be classified into "EBV DNA positive to negative" and "EBV DNA consistently positive" based on the pre-induction and post-induction EBV DNA. Multivariable Cox models, including key tumor and patient characteristics will also be included.
Measured: Up to 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2023
- Study start15 Jul 2024
- Primary completion30 Apr 2029 (estimated)
- Study completion30 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Nasopharyngeal CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 156 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Brigette B Ma, Principal investigator, NRG Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06029270
- Sponsor's protocol ID
- NCI-2023-06678
- Other IDs
- NCI-2023-06678, NRG-HN011, NRG-HN011, U10CA180868
- Status last verified
- Sep 2026
- First submitted
- 7 Sep 2023
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.