Study Evaluating Two Loading Regimens of Sunitinib or Bevacizumab Alternating With Cisplatin and Gemcitabine as Induction Therapy for Locally Advanced Nasopharyngeal Carcinoma (NPC)
Condition: Nasopharyngeal Carcinoma
MeSH terms: Carcinoma; Nasopharyngeal Carcinoma
Study type: Interventional
Phase: Phase 2

Summary: 
      - Hypothesis

      We hypothesise that intermittent dosing of the anti-angiogenic RTKI sunitinib or bevacizumab
      prior to systemic cisplatin and gemcitabine chemotherapy to transiently "normalise" tumour
      vasculature in patients with locally advanced or metastatic NPC will allow greater efficiency
      in drug and oxygen delivery, thus potentiating sensitivity to chemotherapy. We hypothesise
      that a loading dose of sunitinib for 7 days is required to achieve this sensitization effect
      prior to the first cycle of chemotherapy, and that this effect can subsequently be maintained
      by a 7 day course of sunitinib prior to each subsequent cycle of chemotherapy. The other
      hypothesis tested is that bevacizumab 7 days prior to chemotherapy will achieve normalization
      of tumor vasculature as well, and may induce changes in the tumor microenvironment that is
      beneficial for antitumour effect.
    

Detailed description: 
      -  Primary objectives

             1. To determine the pathological CR* rate of intermittent sunitinib or bevacizumab
                administered with combination cisplatin and gemcitabine as systemic therapy for
                locally advanced or metastatic NPC.

             2. To determine the safety and tolerability of intermittent sunitinib or bevacizumab
                administered with combination cisplatin and gemcitabine as systemic therapy for
                locally advanced or metastatic NPC.

        -  Secondary objectives

             1. To determine the clinical RR (complete and partial response)+ of intermittent
                sunitinib or bevacizumab administered with combination cisplatin and gemcitabine as
                systemic therapy for locally advanced or metastatic NPC.

             2. To evaluate the pharmacodynamic effects (imaging, circulating and tissue) of
                intermittent sunitinib or bevacizumab administered with combination cisplatin and
                gemcitabine as systemic therapy for locally advanced or metastatic NPC.

             3. To evaluate the early pharmacodynamic effects (imaging, circulating and tissue) of
                2 loading doses of sunitinib (ie., 12.5mg or 25mg) and 2 dose level of bevacizumab
                (ie. 7.5mg/kg or 2.5mg/kg) given 1 week prior to administration of cisplatin and
                gemcitabine chemotherapy.
    

Intervention name(s): 12.5mg sunitinib with Cisplatin and Gemcitabine; 25mg Sunitinib alternating with Cisplatin and Gemcitabine; 7.5mg/kg Bevacizumab alternating with Cisplatin and Gemcitabine; 2.5mg/kg Bevacizumab alternating with Cisplatin and Gemcitabine
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 1) Arm A
Day -6 to Day 0 (total 7 days):
Sunitinib 12.5mg daily Cycles 1 and 2 - Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2 Day 15 to Day 21: Sunitinib 12.5mg daily Cycle 3 - Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2; Arm B
Day -6 to Day 0 (total 7 days):
Sunitinib 25mg daily Cycles 1 and 2 - Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2 Day 15 to Day 21: Sunitinib 25mg daily Cycle 3 - Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2; Day -7: IV bevacizumab 7.5mg/kg diluted in normal saline over 30 minutes Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2 For locally advanced patients, 3 cycles of treatment will be administered. For metastatic patients, up to 6 cycles would be administered.; Day -7: IV bevacizumab 2.5mg/kg diluted in normal saline over 30 minutes Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2 For locally advanced patients, 3 cycles of treatment will be administered. For metastatic patients, up to 6 cycles would be administered
Other intervention name(s): Arm A; Arm B; Arm C; Arm D
Intervention MeSH terms: Bevacizumab; Sunitinib; Cisplatin; Gemcitabine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: locally advanced; metastatic