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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 | Clinical Trials | Clareo Health

TERMINATEDPHASE3

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

NCT04458909•National Cancer Institute (NCI)

View on ClinicalTrials.gov

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.

Detailed Description

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•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)
+11 more criteria

Exclusion Criteria

•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:
+18 more criteria

Locations (325)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Anchorage Associates in Radiation Medicine