NCT01309633

Study Evaluating Two Loading Regimens of Sunitinib or Bevacizumab Alternating With Cisplatin and Gemcitabine as Induction Therapy for Locally Advanced Nasopharyngeal Carcinoma (NPC)

Phase II Open-label Study Evaluating Two Loading Regimens of Sunitinib or Bevacizumab Alternating With Cisplatin and Gemcitabine as Systemic Therapy for Locally Advanced or Metastatic Nasopharyngeal Carcinoma (NPC)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (actual)
• Sponsor: National University Hospital, Singapore · Academic / Other
• Sex: All
• Age: 21 Years – 99 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Nasopharyngeal Carcinoma

Interventions

Type	Name	Description
DRUG	12.5mg sunitinib with Cisplatin and Gemcitabine	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
DRUG	25mg Sunitinib alternating with Cisplatin and Gemcitabine	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
DRUG	7.5mg/kg Bevacizumab alternating with Cisplatin and Gemcitabine	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.
DRUG	2.5mg/kg Bevacizumab alternating with Cisplatin and Gemcitabine	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

Timeline

• Start date: 2011-09-02
• Primary completion: 2019-03-11
• Completion: 2019-03-11
• First posted: 2011-03-07
• Last updated: 2019-07-22

Locations

1 site across 1 country: Singapore