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)

Antirheumatic Agents

Cyclophosphamide

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients receive oral cyclophosphamide 50 to 150mg daily continuously in the absence of disease progression or unacceptable toxicity.

Patient receive oral cyclophosphamide 50 to 150mg daily continuously in the absence of disease progressive or unacceptable toxicity.

Victor Lee, MD

There is no standard third-line systemic treatment for inoperable locoregionally advanced recurrent or metastatic nasopharyngeal carcinoma (NPC). We investigated the efficacy and safety of metronomic oral cyclophosphamide as third-line treatment or beyond.

NPC is endemic in Southern China including Hong Kong. Despite aggressive definitive chemoradiotherapy for locoregionally advanced disease, still about 30% develop relapse locoregionally or distally. Salvage or second-course radical radiotherapy with or without chemotherapy may achieve durable disease control for locoregionally advanced recurrent disease. However for those who had received 2 courses of radical radiotherapy or those with distant metastases, systemic chemotherapy would be the only drug of choice. Platinum-based doublet chemotherapy including cisplatin + 5-fluorouracil, capecitabine, gemcitabine or taxane is considered the standard first-line treatment. For second-line treatment, whether platinum-based chemotherapy was given previously is a consideration. Re-challenge with cisplatin and 5-fluorouracil can be considered in patients who enjoyed a good initial response to the same regimen with an intervening disease-free period of more than 1 year.However so far there has been no recognized standard third-line systemic treatment. Metronomic oral chemotherapy may provide an ideal choice patients treated in this setting by shifting the targets from tumor cells to tumor vasculature so as to reduce the chance of drug resistance as well as offering a relatively low toxicity profile to them who have been significantly jeopardized by the long-term complications brought prior courses of radiation therapy, surgery and chemotherapy.

In view of the above, we investigated metronomic open-label oral cyclophosphamide as third-line treatment or beyond in patients with inoperable locoregionally advanced recurrent or metastatic NPC who had failed at least 2 lines of prior systemic chemotherapy.

Cyclophosphamide for Nasopharyngeal Carcinoma

Metronomic Oral Cyclosphosphamide as Third-line Systemic Treatment or Beyond in Patients With Inoperable Locoregionally Advanced Recurrent or Metastatic Nasopharyngeal Carcinoma

There is no plan for to make individual participant data available.

Interval between the date of commencement of cyclophosphamide to the date of radiologically confirmed progressive disease or death, whichever comes earlier.

The percentage of patients who demonstrate complete response or partial response after study medication as assessed by RECIST 1.1

The percentage of patients who demonstrate complete response, partial response or stable disease after study medication as assessed by RECIST 1.1

All treatment-related adverse events as assessed by CTCAE version 4.0 will be recorded

Time interval between the date of commencement of cyclophosphamide to the date of death

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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)
Cyclophosphamide for Nasopharyngeal Carcinoma	NCT02794077	Recurrent Nasop... Stage IV Nasoph...	Cyclophosphamid...	15 Years - 80 Years	The University of Hong Kong

Spots Global Cancer Trial Database for recurrent nasopharyngeal undifferentiated carcinoma