NCT04458909|TerminatedPhase 3ResultsDMCFDA Drug

Study Stopped

External information

Testing the Addition of an Anti-cancer Immune Therapy Drug (Nivolumab) to the Usual Chemotherapy Treatment (Cisplatin or Carboplatin With Gemcitabine) for Recurrent or Metastatic Nasopharyngeal Cancer

An Open-Label, Phase III Study of Platinum-Gemcitabine With or Without Nivolumab in the First-Line Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma

National Cancer Institute (NCI)ClinicalTrials.gov

Compare

3 other identifiers

NCI-2020-04581NRG-HN007U10CA180868

Study Type

interventional

Target

Locations

4 countries

Sites

325

Timeline

RegisteredJul 2020

StartedDec 2020

CompletionAug 2023

Brief Summary

This phase III trial compares the effect of adding nivolumab to the usual chemotherapy (cisplatin or carboplatin with gemcitabine) versus standard chemotherapy alone in treating patients with nasopharyngeal cancer that has come back (recurrent) or spread to other places in the body (metastatic). 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. Chemotherapy drugs, such as cisplatin, carboplatin, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab with the usual chemotherapy may work better than the standard chemotherapy alone in treating patients with nasopharyngeal cancer.

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at below P25 for phase_3

Timeline

Completed

Started Dec 2020

Typical duration for phase_3

Geographic Reach

4 countries

325 active sites

Status

terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

2.7 years study duration

First Submitted

Initial submission to the registry

July 1, 2020

Completed

6 days until next milestone

First Posted

Study publicly available on registry

July 7, 2020

Completed

5 months until next milestone

Study Start

First participant enrolled

December 9, 2020

Completed

2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 15, 2023

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 15, 2023

Completed

1.1 years until next milestone

Results Posted

Study results publicly available

September 19, 2024

Completed

Last Updated

October 3, 2025

Status Verified

September 1, 2025

Enrollment Period

2.7 years

First QC Date

July 1, 2020

Results QC Date

August 23, 2024

Last Update Submit

September 16, 2025

Conditions

Metastatic Nasopharyngeal Carcinoma Metastatic Nasopharyngeal Keratinizing Squamous Cell Carcinoma Metastatic Nasopharyngeal Nonkeratinizing Carcinoma Metastatic Nasopharyngeal Undifferentiated Carcinoma Nasopharyngeal Nonkeratinizing Carcinoma Recurrent Nasopharyngeal Carcinoma Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma Recurrent Nasopharyngeal Undifferentiated Carcinoma Stage IV Nasopharyngeal Carcinoma AJCC v8 Stage IVA Nasopharyngeal Carcinoma AJCC v8 Stage IVB Nasopharyngeal Carcinoma AJCC v8

Outcome Measures

Primary Outcomes (1)

Overall Survival (OS)
Failure is death from any cause. Survival rates were to be estimated using the Kaplan-Meier method and arms were to be compared using a log-rank test. Analysis was to occur after 200 deaths have been reported. Given the small number of participants due to early study closure, only the number of patients last reported to be alive at time of study termination is reported.
Baseline to the date of death or last follow-up. Maximum follow-up time was 2.3 years.

Secondary Outcomes (10)

Locoregional Failure
Baseline to the date of failure or last known follow-up. Maximum follow-up time was 2.3 years.
Distant Metastases
Randomization to the date of failure or last known follow-up. Maximum follow-up time was 2.3 years.
Progression-free Survival (PFS)
Baseline to the date of failure or last known follow-up. Maximum follow-up time was 2.3 years.
Number of Participants With Complete or Partial Response (Objective Response Rate) Through the End of Cycle 6 Determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Baseline through end of cycle 6 (each cycle is 21 days)
Number of Participants With Grade 3 or Higher Adverse Events (AEs)
Baseline to the date of last follow-up. Maximum follow-up time was 2.3 years.
+5 more secondary outcomes

Other Outcomes (4)

Overall Survival by PD-L1 CPS and TPS
Baseline to the date of failure or last known follow-up. Maximum follow-up time was 2.3 years.
Change From Baseline to Cycle 6 in Global Heath Status (GHS) Score of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
Baseline and end of cycle 6 (each cycle is 21 days)
Change From Baseline to Cycle 6 in Multidimensional Fatigue Inventory (MFI)-20 Total Score
Baseline and end of cycle 6 (each cycle is 21 days)
+1 more other outcomes

Study Arms (2)

Arm I (nivolumab, gemcitabine, cisplatin / carboplatin)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes on day 1, gemcitabine IV over 30 minutes on days 1 and 8, and cisplatin IV over 30-60 minutes or carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 4 weeks, patients then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Drug: CarboplatinDrug: CisplatinDrug: GemcitabineBiological: NivolumabOther: Questionnaire Administration

Arm II (gemcitabine, cisplatin / carboplatin)

ACTIVE COMPARATOR

Patients receive gemcitabine and cisplatin or carboplatin as in Arm I.

Drug: CarboplatinDrug: CisplatinDrug: GemcitabineOther: Questionnaire Administration

Interventions

CarboplatinDRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Arm I (nivolumab, gemcitabine, cisplatin / carboplatin)Arm II (gemcitabine, cisplatin / carboplatin)

CisplatinDRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Arm I (nivolumab, gemcitabine, cisplatin / carboplatin)Arm II (gemcitabine, cisplatin / carboplatin)

GemcitabineDRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Arm I (nivolumab, gemcitabine, cisplatin / carboplatin)Arm II (gemcitabine, cisplatin / carboplatin)

NivolumabBIOLOGICAL

Given IV

Also known as: ABP 206, BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Arm I (nivolumab, gemcitabine, cisplatin / carboplatin)

Questionnaire AdministrationOTHER

Ancillary studies

Arm I (nivolumab, gemcitabine, cisplatin / carboplatin)Arm II (gemcitabine, cisplatin / carboplatin)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Pathologically (histologically or cytologically) proven diagnosis of NPC that has recurred at locoregional and/or distant sites. For locoregional recurrence, the disease must not be amenable to potentially curative surgery or re-irradiation. The following histological types are accepted: (a) Keratinizing - squamous cell carcinoma; (b) Non-keratinizing - undifferentiated or poorly differentiated
Measurable disease by the RECIST 1.1 criteria. Lesion(s) that have been irradiated previously can be counted as measurable as long as radiological progression has been demonstrated prior to enrollment
History/physical examination by a medical oncologist or clinical oncologist within 14 days prior to registration
Zubrod/Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 14 days prior to registration
Contrast enhanced magnetic resonance imaging (MRI) or computed tomography (CT) of the nasopharynx and neck within 30 days prior to registration
Contrast enhanced CT scan of the chest, abdomen, and pelvis within 30 days prior to registration
Absolute neutrophil count (ANC) \>= 1500 cells/mm\^3 (within 14 days prior to registration)
Platelets \>= 100,000 cells/mm\^3 (within 14 days prior to registration)
Hemoglobin \>= 9.0 g/dL (transfusion is accepted. Erythropoietin dependency not accepted) (within 14 days prior to registration)
Total bilirubin =\< 1.5 x upper limit of normal (ULN) OR direct bilirubin =\< ULN for patients with total bilirubin levels \> 1.5 x ULN. Patients with known Gilbert's syndrome are not excluded (within 14 days prior to registration)
Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN (=\< 3 x ULN for patients with liver metastases) (within 14 days prior to registration)
Serum creatinine =\< 1.5 x ULN OR calculated creatinine clearance (CrCl) based on Cockcroft-Gault equation \>= 30 mL/min for patients with serum creatinine levels \> 1.5 x ULN. In this protocol, 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 (within 14 days prior to registration)
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable, and patients must be receiving anti-viral therapy at enrollment. Patients must agree to continue anti-viral therapy throughout the study period as directed by their treating physicians
Known positive test for hepatitis B virus surface antigen (HBsAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on anti-viral therapy
Patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (i.e., patients immunized against hepatitis B)
+7 more criteria

You may not qualify if:

Diagnosed with another invasive malignancy (except non-melanomatous skin cancer) unless disease free for more than 3 years. Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) who have undergone potentially curative therapy are not excluded
Any prior systemic anti-cancer agents (including chemotherapy and investigational agents) for the purpose of treating locoregional and/or distant recurrence of NPC
Patients who have received neoadjuvant (induction) and/or adjuvant chemotherapy for primary NPC with chemotherapy (any drug regimens including those containing platinum and/or gemcitabine) at or within 6 months prior to registration are excluded (counting from the last day of the chemotherapy for the primary NPC, prior to enrolling into the current study). The following subgroups of patients are NOT excluded:
Patients who have received neoadjuvant (induction) and/or adjuvant chemotherapy for primary (non-metastatic/non-recurrent) NPC more than 6 months prior to registration, counting from the last day of the chemoradiotherapy for the primary NPC, prior to enrolling into the current study
For prior RT with radical intent: Patients who have prior radiotherapy (RT) to the primary and locoregional disease (i.e. non-recurrent disease) with or without concurrent cisplatin or carboplatin monotherapy are not excluded as long as they have not received any neoadjuvant/adjuvant chemotherapy within 6 months prior to registration (counting from the last day of the chemotherapy), and that the last RT fraction (with radical intent) has been given more than 3 months prior to registration
For RT with palliative intent: Prior radiotherapy (RT) at or within 30 days prior to registration, this includes RT given with palliative intent (with or without concurrent cisplatin or carboplatin alone) to recurrent/ metastatic sites in patients with recurrent/metastatic NPC. The re-irradiated sites must not be the only sites of measurable recurrent disease
Prior chemotherapy for cancers other than NPC is allowed as long as the last course of chemotherapy was administered more than 3 years prior to registration and the patient has remained disease-free for more than 3 years
Prior therapy for any indication, with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137)
History of severe (grade 3-4) hypersensitivity reaction to any monoclonal antibody including nivolumab and/or any of its excipients
Severe, active co-morbidity defined as follows:
Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
Myocardial infarction within the last 6 months
Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration
Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
+13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead
NRG Oncologycollaborator

Study Sites (325)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC