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

Official Title

An Open-Label, Phase III Study of Platinum-Gemcitabine With or Without Nivolumab in the First-Line Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma

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 tumour cells to grow and spread. Chemotherapy drugs, such as cisplatin, carboplatin, and gemcitabine, work in different ways to stop the growth of tumour 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.

Trial Description

Primary Outcome:

• Overall survival (OS)

Secondary Outcome:

• Locoregional failure
• Distant metastases
• Progression-free survival (PFS)
• Tumour response
• Incidence of adverse events (AEs)
• Patient-reported symptomatic toxicities
• Quality of life
• Fatigue
• Progression-free survival by PD-L1 Combined Positive Score (CPS)/Tumour Proportion Score (TPS) cut-off

PRIMARY OBJECTIVE:

• 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:

• To compare patterns of failure (local-regional relapse and distant metastasis) between treatment arms.
• To determine if adding nivolumab to platinum-gemcitabine as first-line treatment improves the objective tumour response based on Response Evaluation Criteria in Solid Tumours (RECIST) 1.1.
• 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.
• To evaluate the toxicity based on the Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
• To characterize patient-reported symptomatic toxicities measured by Patient-Reported Outcomes (PRO)-CTCAE.
• 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).
• To assess fatigue, as measured by Multidimensional Fatigue Inventory (MFI-20), between the two arms (secondary PRO).
• To determine if a subset of patients based on an optimal cutoff point of PD-L1 Combined Positive Score (CPS)/Tumour Proportion Score (TPS) is more likely to benefit in terms of PFS from adding nivolumab to platinum-gemcitabine as first-line treatment.

EXPLORATORY OBJECTIVES:

• 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.
• 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).
• 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 60 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.

View this trial on ClinicalTrials.gov