NCT04458909

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

Terminated Phase 3 Results posted Last updated 3 October 2025

What this trial tests

Phase 3 trial testing Carboplatin in Metastatic Nasopharyngeal Carcinoma in 15 participants. Terminated before completion.

Timeline

9 December 2020

Primary endpoint
15 August 2023

15 August 2023

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	15
Start date	9 December 2020
Primary completion	15 August 2023
Estimated completion	15 August 2023
Sites	325 locations across China, Singapore, Canada, United States

Drugs / interventions tested

• Carboplatin (Carboplatin) — full drug profile →
• Cisplatin (cisplatin) — full drug profile →
• Gemcitabine (gemcitabine) — full drug profile →
• Nivolumab (nivolumab) — full drug profile →
• Questionnaire Administration

Conditions studied

• Metastatic Nasopharyngeal Carcinoma — all drugs for Metastatic Nasopharyngeal Carcinoma →
• Metastatic Nasopharyngeal Keratinizing Squamous Cell Carcinoma — all drugs for Metastatic Nasopharyngeal Keratinizing Squamous Cell Carcinoma →
• Metastatic Nasopharyngeal Nonkeratinizing Carcinoma — all drugs for Metastatic Nasopharyngeal Nonkeratinizing Carcinoma →
• Metastatic Nasopharyngeal Undifferentiated Carcinoma — all drugs for Metastatic Nasopharyngeal Undifferentiated Carcinoma →

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Metastatic Nasopharyngeal Carcinoma or Metastatic Nasopharyngeal Keratinizing Squamous Cell Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Survival (OS) Primary · Baseline to the date of death or last follow-up. Maximum follow-up time was 2.3 years.

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.

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	8
Arm II (Gemcitabine, Cisplatin / Carboplatin)	4

Locoregional Failure Secondary · Baseline to the date of failure or last known follow-up. Maximum follow-up time was 2.3 years.

Locoregional failure is defined as first evidence of local or regional progression, death due to study cancer without documented progression, or death due to unknown causes without documented progression; distant metastasis and deaths from other causes were considered competing risks. Progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 is defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance or recurrence of any locoregional lesions is also considered progression. Failure rates were

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	6
Arm II (Gemcitabine, Cisplatin / Carboplatin)	0

Distant Metastases Secondary · Randomization to the date of failure or last known follow-up. Maximum follow-up time was 2.3 years.

Distant failure is defined as first evidence of distant metastasis; locoregional failure and all deaths were to be considered competing risks. Distant failure rates were to be estimated using the cumulative incidence method and arms were to be compared using the cause-specific log-rank test. Analysis was to occur after 200 deaths. Given the small number of participants due to early study closure, only the number of patients with distant failure is reported.

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	2
Arm II (Gemcitabine, Cisplatin / Carboplatin)	1

Progression-free Survival (PFS) Secondary · Baseline to the date of failure or last known follow-up. Maximum follow-up time was 2.3 years.

Failure is defined as local, regional, or distant disease progression, or death from any cause. Progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 is defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance or recurrence of any lesions is also considered progression. Failure rates were to be estimated using the Kaplan-Meier method and arms were to be compared using the log-rank test. Analysis was to occur after 200 deaths. Given the small number of participants due to early study closu

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	3
Arm II (Gemcitabine, Cisplatin / Carboplatin)	3

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 Secondary · Baseline through end of cycle 6 (each cycle is 21 days)

CT/MRI of nasopharynx and neck or chest CT at baseline and through the end of cycle 6 are compared to determine tumor response. Per RECIST 1.1: * Complete response: * Disappearance of all lesions and pathologic lymph nodes * Partial response: * 30% decrease sum of the longest diameters * No new lesions * No progression of non-target lesions

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	4
Arm II (Gemcitabine, Cisplatin / Carboplatin)	0

Number of Participants With Grade 3 or Higher Adverse Events (AEs) Secondary · Baseline to the date of last follow-up. Maximum follow-up time was 2.3 years.

Common Terminology Criteria for Adverse Events (CTCAE) version 5 grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. Counts of participants with any grade 3 or higher adverse event are reported. Adverse events of any attribution are included.

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	10
Arm II (Gemcitabine, Cisplatin / Carboplatin)	2

Number of Participants With Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) Severity Score ≥ 3 (or Present) at Baseline Secondary · Baseline

PRO-CTCAE is a patient-reported outcome (PRO) measurement system developed to evaluate symptomatic toxicity in patients on cancer clinical trials. This study collects PRO-CTCAE data on sixteen symptomatic adverse events (AEs), asking about experience over the last seven days. Worst severity of the given symptom was collected for 14 items (0=none, 1=mild, 2=moderate, 3=severe, and 4=very severe). Any presence of the symptom was collected for 2 items (present/absent). For each symptom, the row label indicates whether severity score ≥ 3 or presence is reported.

Dry mouth (severity grade 3+)

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	1
Arm II (Gemcitabine, Cisplatin / Carboplatin)	1

Difficulty swallowing (severity grade 3+)

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	1
Arm II (Gemcitabine, Cisplatin / Carboplatin)	0

Voice quality changes (presence)

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	2
Arm II (Gemcitabine, Cisplatin / Carboplatin)	0

Mouth/throat sore (severity grade 3+)

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	0
Arm II (Gemcitabine, Cisplatin / Carboplatin)	0

Taste changes (severity grade 3+)

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	0
Arm II (Gemcitabine, Cisplatin / Carboplatin)	0

Abdominal pain (severity grade 3+)

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	0
Arm II (Gemcitabine, Cisplatin / Carboplatin)	0

Heart palpitations (severity grade 3+)

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	0
Arm II (Gemcitabine, Cisplatin / Carboplatin)	1

Rash (presence)

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	1
Arm II (Gemcitabine, Cisplatin / Carboplatin)	0

Number of Participants With Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) Severity Score ≥ 3 (or Present) at Cycle 6 Secondary · End of cycle 6 (each cycle is 21 days for the first six cycles)

PRO-CTCAE is a patient-reported outcome (PRO) measurement system developed to evaluate symptomatic toxicity in patients on cancer clinical trials. This study collects PRO-CTCAE data on sixteen symptomatic adverse events (AEs), asking about experience over the last seven days. Worst severity of the given symptom was collected for 14 items (0=none, 1=mild, 2=moderate, 3=severe, and 4=very severe). Any presence of the symptom was collected for 2 items (present/absent). For each symptom, the row label indicates whether severity score ≥ 3 or presence is reported.

Dry mouth (severity grade 3+)

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	1
Arm II (Gemcitabine, Cisplatin / Carboplatin)	0

Difficulty swallowing (severity grade 3+)

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	0
Arm II (Gemcitabine, Cisplatin / Carboplatin)	0

Voice quality changes (presence)

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	1
Arm II (Gemcitabine, Cisplatin / Carboplatin)	0

Mouth/throat sore (severity grade 3+)

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	1
Arm II (Gemcitabine, Cisplatin / Carboplatin)	0

Taste changes (severity grade 3+)

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	0
Arm II (Gemcitabine, Cisplatin / Carboplatin)	0

Abdominal pain (severity grade 3+)

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	0
Arm II (Gemcitabine, Cisplatin / Carboplatin)	0

Heart palpitations (severity grade 3+)

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	0
Arm II (Gemcitabine, Cisplatin / Carboplatin)	0

Rash (presence)

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	1
Arm II (Gemcitabine, Cisplatin / Carboplatin)	0

Global Heath Status (GHS) Score of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Secondary · End of cycle 6 (each cycle is 21 days)

Global Health Status is calculated from two questions on the EORTC QLQ-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best).

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	63.9	± 9.6
Arm II (Gemcitabine, Cisplatin / Carboplatin)	75.0	± 4.8

Multidimensional Fatigue Inventory (MFI)-20 Total Score Secondary · End of cycle 6 (each cycle is 21 days)

The MFI-20 is a 20-item self-report instrument measuring fatigue with the total score ranging from 20 to 100 and a higher score indicating more fatigue.

Group	Value	95% CI
Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)	61.6	± 4.4
Arm II (Gemcitabine, Cisplatin / Carboplatin)	72.7	± 7.8

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline to the date of failure or last known follow-up. Maximum follow-up time was 2.3 years.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm I (Nivolumab, Gemcitabine, Cisplatin / Carboplatin)

Serious: 10/11 (91%)

Deaths: 3/11

Arm II (Gemcitabine, Cisplatin / Carboplatin)

Serious: 2/4 (50%)

Deaths: 0/4

Serious adverse events (13 terms)

Reaction	System	Arm I (Nivolumab, Gemcitab…	Arm II (Gemcitabine, Cispl…
Neutrophil count decreased	Investigations	—	—
Anemia	Blood and lymphatic system disorders	—	—
Dysphagia	Gastrointestinal disorders	—	—
Mucositis oral	Gastrointestinal disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Alkaline phosphatase increased	Investigations	—	—
Platelet count decreased	Investigations	—	—
White blood cell decreased	Investigations	—	—
Dehydration	Metabolism and nutrition disorders	—	—
Hyponatremia	Metabolism and nutrition disorders	—	—
Syncope	Nervous system disorders	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
Hypertension	Vascular disorders	—	—

Other adverse events (100 terms — click to expand)

Reaction	System	Arm I (Nivolumab, Gemcitab…	Arm II (Gemcitabine, Cispl…
Fatigue	General disorders	—	—
Neutrophil count decreased	Investigations	—	—
Constipation	Gastrointestinal disorders	—	—
Anemia	Blood and lymphatic system disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Insomnia	Psychiatric disorders	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—
Dysphagia	Gastrointestinal disorders	—	—
Anorexia	Metabolism and nutrition disorders	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Mucositis oral	Gastrointestinal disorders	—	—
Fever	General disorders	—	—
Platelet count decreased	Investigations	—	—
Weight loss	Investigations	—	—
White blood cell decreased	Investigations	—	—
Hypomagnesemia	Metabolism and nutrition disorders	—	—
Hyponatremia	Metabolism and nutrition disorders	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Blood and lymphatic system disorders - Other	Blood and lymphatic system disorders	—	—
Hearing impaired	Ear and labyrinth disorders	—	—
Hypothyroidism	Endocrine disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Dry mouth	Gastrointestinal disorders	—	—
Toothache	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Edema limbs	General disorders	—	—
Bruising	Injury, poisoning and procedural complications	—	—
Alanine aminotransferase increased	Investigations	—	—
Alkaline phosphatase increased	Investigations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Creatinine increased	Investigations	—	—
Dehydration	Metabolism and nutrition disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Neck pain	Musculoskeletal and connective tissue disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Dizziness	Nervous system disorders	—	—
Dysgeusia	Nervous system disorders	—	—
Headache	Nervous system disorders	—	—

Most-reported serious reactions: Neutrophil count decreased, Anemia, Dysphagia, Mucositis oral, Alanine aminotransferase increased, Alkaline phosphatase increased, Platelet count decreased, White blood cell decreased.

Data from ClinicalTrials.gov NCT04458909 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Nasopharyngeal carcinoma: current views on the tumor microenvironment's impact on drug resistance and clinical outcomes.
   Liu H, Tang L, Li Y, Xie W, et al · · 2024 · cited 85× · PMID 38254110 · DOI 10.1186/s12943-023-01928-2
2. Gemcitabine Plus Cisplatin Versus Fluorouracil Plus Cisplatin as First-Line Therapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: Final Overall Survival Analysis of GEM20110714 Phase III Study.
   Hong S, Zhang Y, Yu G, Peng P, et al · · 2021 · cited 81× · PMID 34379443 · DOI 10.1200/jco.21.00396
3. Immunotherapy for nasopharyngeal carcinoma: Current status and prospects (Review).
   Huang H, Yao Y, Deng X, Huang Z, et al · · 2023 · cited 78× · PMID 37417358 · DOI 10.3892/ijo.2023.5545
4. Recurrent/Metastatic Nasopharyngeal Carcinoma Treatment from Present to Future: Where Are We and Where Are We Heading?
   Juarez-Vignon Whaley JJ, Afkhami M, Onyshchenko M, Massarelli E, et al · · 2023 · cited 71× · PMID 37318724 · DOI 10.1007/s11864-023-01101-3
5. Current status and advances of immunotherapy in nasopharyngeal carcinoma.
   Xu JY, Wei XL, Wang YQ, Wang FH. · · 2022 · cited 62× · PMID 35547095 · DOI 10.1177/17588359221096214
6. Targeting Metabolic Vulnerabilities in Epstein-Barr Virus-Driven Proliferative Diseases.
   Leung NYT, Wang LW. · · 2023 · cited 4× · PMID 37444521 · DOI 10.3390/cancers15133412
7. Best practices and pragmatic approaches for patient-reported outcomes and quality of life measures in cancer clinical trials.
   Bandos H, Torres-Saavedra PA, Culakova E, Gunn HJ, et al · · 2025 · cited 2× · PMID 39989038 · DOI 10.1093/jncimonographs/lgae047
8. Pembrolizumab (MK-3475) plus platinum and gemcitabine as first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (PIPER): a phase 2, multicentre, single-arm protocol study in Malaysia.
   Cheong SC, Selvam B, Ho GF, Muhamad Nor I, et al · · 2024 · cited 1× · PMID 39627139 · DOI 10.1136/bmjopen-2023-076898