Neoplasms

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Nasopharyngeal Carcinoma

Recurrence

Carcinoma

Carcinoma, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Neoplasms, Squamous Cell

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Nivolumab

Carboplatin

Cisplatin

Antimetabolites

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

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

Questionnaire Administration

Brigette B Ma

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.

PRIMARY OBJECTIVE:

I. To determine if adding nivolumab to platinum-gemcitabine as first-line treatment improves overall survival (OS) for patients with recurrent and/or metastatic nasopharyngeal carcinoma (NPC).

SECONDARY OBJECTIVES:

I. To compare patterns of failure (local-regional relapse and distant metastasis) between treatment arms.

II. To determine if adding nivolumab to platinum-gemcitabine as first-line treatment improves the objective tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

III. To determine if adding nivolumab to platinum-gemcitabine as first-line treatment improves progression free survival (PFS) for patients with recurrent and/or metastatic NPC.

IV. To evaluate the toxicity based on the Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.

V. To characterize patient-reported symptomatic toxicities measured by Patient-Reported Outcomes (PRO)-CTCAE.

VI. To assess the quality of life (QOL), as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Core (C)30, between the two arms (primary PRO).

VII. To assess fatigue, as measured by Multidimensional Fatigue Inventory (MFI-20), between the two arms (secondary PRO).

VIII. To determine if a subset of patients based on an optimal cutoff point of PD-L1 Combined Positive Score (CPS)/Tumor Proportion Score (TPS) is more likely to benefit in terms of PFS from adding nivolumab to platinum-gemcitabine as first-line treatment.

EXPLORATORY OBJECTIVES:

I. To determine if a subset of patients based on an optimal cutoff point of PD-L1 CPS/TPS is more likely to benefit in terms of overall survival (OS) from adding nivolumab to platinum-gemcitabine as first-line treatment.

II. To determine changes in QOL as measured by EORTC QLQ-C30 and in fatigue as measured by MFI-20, between and within arms over time (exploratory PRO).

III. To collect blood and tissue specimens for future translational research.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive nivolumab intravenously (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.

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

After completion of study treatment, patients are followed up every 4 months for 2 years, every 6 months for 3 years, and then annually.

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

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.

Will be assessed based on PD-L1 CPS/TPS cut-off.

Will be measured by EORTC QLQ-C30 between and within arms over time.

Will be measured by MFI-20 between and within arms over time.

Overall survival rates for both treatment arms will be estimated using the Kaplan-Meier method. The comparison of OS distributions between treatment arms will be done using a log-rank test.

Rates estimated by cumulative incidence method and arms compared by cause-specific log-rank test.

Rates estimated using the Kaplan-Meier method and between-arm differences compared using the log-rank test.

Will be assessed by Response Evaluation Criteria in Solid Tumors 1.1. The Objective Response Rate (ORR), defined as the proportion of confirmed complete and partial response, will be calculated with their respective 95% confidence intervals (CI). An estimate of the difference in ORR between the experimental and control arms along with the 95% CI, will also be provided. The between-arm difference in ORR will be assessed using a chi-square test for proportions based on normal approximation. The confidence intervals will be also based on a normal approximation.

Will be assessed by Common Terminology Criteria for Adverse Events version 5.0. Counts of all AEs by grade will be provided by the treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient's treatment arm. The number of patients with at least 1 grade 3 or higher AE will be compared between the treatment arms. All comparisons will be tested using a chi-Square test, or Fisher's exact test if cell frequencies are \< 5, with a significance level of 0.05. Toxicity analyses will be based on an as-treated population, including all patients who received at least one dose of the assigned trial treatment.

Will be assessed by Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE). The proportion of patients with scores \>= 1 and \>= 3 will be compared between groups using a Chi-square test, or Fisher's exact test if cell frequencies are \< 5, using a significance level of 0.05. Analysis of changes in patient reported outcomes over time will be analyzed by fitting generalized estimating equation (GEE) models using a logit link (dichotomizing the symptom scores as 0 versus \[vs.\] \> 1 and 0-2 vs. 3-4) with the time of assessment, treatment arm, and treatment-by-time interaction terms in the model.

Will be assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30).

Will be assessed by Multidimensional Fatigue Inventory (MFI-20).

NRG Oncology

National Cancer Institute (NCI)

Patients receive nivolumab IV over approximately 60 minutes on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

This phase II trial studies how well nivolumab works in treating patients with nasopharyngeal cancer that has returned after a period of improvement (recurrent) and/or has spread to other parts of the body (metastatic). Monoclonal antibodies, such as nivolumab, may block tumor growth in different ways by targeting certain cells.

PRIMARY OBJECTIVES:

I. Objective tumor response to nivolumab in patients with previously treated recurrent and/or metastatic nasopharyngeal carcinoma (NPC) based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.

SECONDARY OBJECTIVES:

I. Tumor response to nivolumab based on immune-related response criteria (IRC). II. Duration of response. III. Progression-free survival and overall survival. IV. Safety and tolerability.

TERTIARY OBJECTIVES:

I. To investigate the effect of nivolumab on tumor burden by analyzing the clearance of plasma Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) during the first 4-6 weeks of treatment.

II. To investigate the association between treatment outcome and immunological markers: a) Intratumoral expression of programmed cell death 1 (PD-1) and programmed cell death-ligand (PD-L1) in archived NPC tissues (mandatory); b) Serum absolute lymphocyte count at baseline and post-treatment (mandatory); and c) Plasma cytokine levels at baseline and serially during the first 8 weeks of treatment; d) Expression of PD-1 in cluster of differentiation (CD)8+ T cells in tumor infiltrating lymphocytes (TIL) at baseline (optional).

III. To investigate functional magnetic resonance imaging (MRI) sequences as an early predictor of response to nivolumab (optional only at Chinese University of Hong Kong \[CUHK\]).

OUTLINE:

Patients receive nivolumab intravenously (IV) over approximately 60 minutes on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 years.

Nivolumab in Treating Patients With Recurrent and/or Metastatic Nasopharyngeal Cancer

Multicenter Phase II Study of Nivolumab in Previously Treated Patients With Recurrent and Metastatic Nasopharyngeal Carcinoma

Plasma EBV DNA half-life during the first 6 weeks of treatment will be correlated with RECIST-response to nivolumab.

PD-1 and PD-L1 expression will be associated with treatment outcomes. The Chi-Square (or Fisher's Exact test) will be used to assess the association of categorical clinical data with categorical biomarker data. Time-to-event clinical data (PFS, OS) will be correlated with biomarker data using Kaplan-Meier methodology and Cox regression models. Logistic regression models will also be used to predict binary clinical data with baseline biomarker data. Finally, graphical methods and descriptive statistics will be used to summarize the data as well.

The Chi-Square (or Fisher's Exact test) will be used to assess the association of categorical clinical data with categorical biomarker data. Time-to-event clinical data (PFS, OS) will be correlated with biomarker data using Kaplan-Meier methodology and Cox regression models. Logistic regression models will also be used to predict binary clinical data with baseline biomarker data. Finally, graphical methods and descriptive statistics will be used to summarize the data as well.

Graphical methods and descriptive statistics will be used.

Confirmed response rate is defined as either a Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1. \> To be consider a CR, there must be a disappearance of all target lesions and each target lymph node must have reduction in short axis to \< 1.0 cm.\> \> To be considered a PR, at least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the baseline value.\>

\> The confirmed response rate is reported as the number of patients reporting a CR or PR divided by the total number of evaluable patients multiplied by 100 (reported as a percentage).

Adverse events were collected and recorded according to the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns. For this outcome measure, we summarize the worst graded adverse event regardless of treatment attribution per patient. All reported adverse events are reported in the Adverse Events section of this report.

The Immune Response Criteria (IRC) is a response criteria derived from the WHO criteria.

Duration of response defined as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented, assessed according to RECIST version 1.1.

Progression Free Survival is defined as the time from registration to the time of death or progression, whichever occurs first. The distribution of PFS will be estimated using the method of Kaplan-Meier.

Overall survival is defined as the time from registration to the time of death. The distribution of survival time will be estimated using the method of Kaplan-Meier.

Adverse events were recorded after every 28 day cycle, up to 42 cycles.

Patients receive 3 mg/kg nivolumab IV over approximately 60 minutes on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Treatment (Nivolumab)

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Singapore

United States

China

Region of Enrollment

All patients that registered for protocol treatment are included in this analysis.

Brigette B.Y. Ma

One patient was a protocol violation and was not included in this analysis.

Confirmed Response Rate (Complete Response or Partial Response) Based on RECIST Version 1.1

Grade 3 or higher

Grade 4 or higher

Grade 5

All patients that began protocol treatment are included in this analysis.

Adverse Events

Data was not collected to analyze this secondary endpoint.

Tumor Response to Nivolumab Based on the Immune Response Criteria (IRC)

All patients that reported a CR or PR on treatment were included in this analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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	NCT04458909	Metastatic Naso... Metastatic Naso... Metastatic Naso... Metastatic Naso... Nasopharyngeal ... Recurrent Nasop... Recurrent Nasop... Recurrent Nasop... Stage IV Nasoph... Stage IVA Nasop... Stage IVB Nasop...	Carboplatin Cisplatin Gemcitabine Nivolumab Questionnaire A...	18 Years -	National Cancer Institute (NCI)
Nivolumab in Treating Patients With Recurrent and/or Metastatic Nasopharyngeal Cancer	NCT02339558	Nasopharyngeal ... Recurrent Nasop... Stage III Nasop... Stage IV Nasoph... Stage IVA Nasop... Stage IVB Nasop... Stage IVC Nasop...	Laboratory Biom... Nivolumab	18 Years -	National Cancer Institute (NCI)
Nivolumab in Treating Patients With Recurrent and/or Metastatic Nasopharyngeal Cancer	NCT02339558	Nasopharyngeal ... Recurrent Nasop... Stage III Nasop... Stage IV Nasoph... Stage IVA Nasop... Stage IVB Nasop... Stage IVC Nasop...	Laboratory Biom... Nivolumab	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for nasopharyngeal nonkeratinizing carcinoma