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 Programmed Death Receptor Ligand-1 (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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Given IV
Given IV
Given IV
Given IV
Ancillary studies
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Anchorage Associates in Radiation Medicine
Anchorage, Alaska, United States
Anchorage Radiation Therapy Center
Anchorage, Alaska, United States
Alaska Breast Care and Surgery LLC
Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
Anchorage, Alaska, United States
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.
Time frame: Baseline to the date of death or last follow-up. Maximum follow-up time was 2.3 years.
Locoregional Failure
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 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 locoregional failure is reported.
Time frame: Baseline to the date of failure or last known follow-up. Maximum follow-up time was 2.3 years.
Distant Metastases
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.
Time frame: Randomization to the date of failure or last known follow-up. Maximum follow-up time was 2.3 years.
Progression-free Survival (PFS)
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 closure, only the number of patients alive without progression is reported.
Time frame: 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
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
Time frame: Baseline through end of cycle 6 (each cycle is 21 days)
Number of Participants With Grade 3 or Higher Adverse Events (AEs)
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.
Time frame: Baseline to the date of last follow-up. Maximum follow-up time was 2.3 years.
Number of Participants With Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) Severity Score ≥ 3 (or Present) at 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.
Time frame: Baseline
Number of Participants With Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) Severity Score ≥ 3 (or Present) at Cycle 6
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.
Time frame: End of cycle 6 (each cycle is 21 days for the first six cycles)
Global Heath Status (GHS) Score of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
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).
Time frame: End of cycle 6 (each cycle is 21 days)
Multidimensional Fatigue Inventory (MFI)-20 Total Score
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.
Time frame: End of cycle 6 (each cycle is 21 days)
Progression-free Survival by Programmed Death Receptor Ligand-1 (PD-L1) Combined Positive Score (CPS) and Tumor Proportion Score (TPS)
This study hypothesizes that the use of PD-L1 expression based on the TPS or CPS may be useful in identifying those patients who are more likely to benefit from treatment with PD-1 inhibitor in combination with chemotherapy. This study will explore a range of CPS and TPS scores.
Time frame: Baseline to the date of failure or last known follow-up. Maximum follow-up time was 2.3 years.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Alaska Women's Cancer Care
Anchorage, Alaska, United States
Anchorage Oncology Centre
Anchorage, Alaska, United States
Katmai Oncology Group
Anchorage, Alaska, United States
Providence Alaska Medical Center
Anchorage, Alaska, United States
Cancer Center at Saint Joseph's
Phoenix, Arizona, United States
...and 315 more locations