The investigators hypothesize that the addition of bevacizumab and pembrolizumab to induction cisplatin and gemcitabine is tolerable and improves metabolic complete response (mCR), relapse free survival (RFS) and overall survival (OS) compared to induction cisplatin and gemcitabine in patients with locally advanced nasopharyngeal cancer (NPC)
The participant (or legally acceptable representative if applicable) provides written consent for the trial.
Participants who are at least 21 years of age on the day of signing informed consent with histologically or cytologically confirmed diagnosis of non-keratinizing nasopharyngeal carcinoma (NPC).
Have measurable disease based on RECIST 1.1.
Tumour stage III (except for T3N0 and T3N1) or IVA according to the American Joint Committee on Cancer (AJCC) 8th edition criteria.
Stage III NPC with T3N0 or T3N1 staged by AJCC 8th edition
Has received prior systemic anti-cancer therapy including chemotherapy, radiotherapy, immunotherapy or investigational agents
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to first dose of study treatment.
Has a condition requiring systemic steroid therapy (> 10 mg daily prednisone equivalents) or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment. Inhaled or topical steroids and adrenal replacement doses <10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if < or = 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
Parallel
cisplatin and gemcitabine
DrugDay 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2
induction chemotherapy cisplatin, gemcitabine, bevacizumab and pembrolizumab.
DrugDay -7 (+/-1 day): IV bevacizumab 7.5mg/kg diluted in normal saline over 30 minutes Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2+ IV pembrolizumab 200mg over 30 minutes Day 8: IV Gemcitabine 1000mg/m2 Day 15 (for cycles 1 and 2 only): IV bevacizumab 7.5mg/kg diluted in normal saline over 30 minutes
metabolic complete response assessed using FDG PET whole body scan at 12 weeks of assessment using PERCIST 1.0
Number of participant with treatment related toxicities
Safety of induction cisplatin, gemcitabine, pembrolizumab and bevacizumab, compared to induction cisplatin and gemcitabine, using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Best objective response rate (ORR) as assessed using Response Evaluation Criteria in Solid Tumour (RECIST 1.1)
Disease free survival (DFS) of patients as defined as the time from initiation of treatment to disease recurrence, or death.
Overall survival of patients, as defined as the time from initiation of treatment to death.
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