NCT00992121

An Open-Label Pharmacodynamic Study of Bevacivumab and Pazopanib in Renal Cell Carcinoma

An Open-Label Study to Investigate the Pharmacodynamics of a Repeat Dose Regimen of Bevacizumab (10 mg/kg q2w) and Escalating Repeat Doses of Pazopanib in Renal Cell Carcinoma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 11 (actual)
• Sponsor: GlaxoSmithKline · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will determine whether blood tests, tumour imaging and tumour tissue analysis can reveal effects of drugs that block blood vessel growth (angiogenesis) in patients with renal cancer.

Detailed description

This single-centre, two-part, open-label study is designed to evaluate pharmacodynamic (PD) effects of bevacizumab and pazopanib in subjects with renal cancer who experience disease progression following at least one prior therapy of documented clinical benefit. In Part I, subjects will receive 3 infusions of 10 mg/kg bevacizumab, administered at 2-week intervals. The PD response to bevacizumab will be evaluated over 6 weeks using imaging techniques (magnetic resonance imaging; computed tomography \[CT\]; and positron emission tomography), intratumoural VEGF signaling by immunohistochemisty, plasma and serum biomarkers, and circulating tumour cells. Subjects may continue into Part II if, in the opinion of the investigator, the subject would derive continued clinical benefit from anti-angiogenic therapy. In Part II, each subject will receive sequentially escalating doses of oral pazopanib in 3-week cycles as follows: 1) 200 mg twice weekly, 2) 200 mg every other day, 3) 200 mg daily, 4) 400 mg daily, 5) 800 mg daily, and 6) 1200 mg daily. Subjects entering Part II will be randomised to receive treatment either throughout each 3-week cycle (Group 1) or for the first 2 weeks of each cycle only, followed by a 1 week treatment holiday (Group 2). After completion of Part II dose escalation subjects will receive continuous pazopanib at a dose of 800 mg daily in repeating 3-week cycles. These subjects will receive pazopanib until loss of clinical benefit, death, unacceptable toxicity, or withdrawal from the study for other reasons.

Conditions

• Carcinoma, Renal Cell

Interventions

Type	Name	Description
DRUG	Bevacizumab	Bevacizumab - 3 infusions of 10mg/kg administered at 2 week intervals - Part I
DRUG	Pazopanib 2 week	Pazopanib for first 2 weeks of each 3-week cycles as follows: 1) 200 mg twice weekly, 2) 200 mg every other day, 3) 200 mg qd, 4) 400 mg qd, 5) 800 mg qd, and 6) 1200 mg qd (Group 1). Maintenance pazopanib 800 mg qd for all 3 weeks throughout repeating 3-week cycles. Number of cycles: until death, loss of clinical benefit, unacceptable toxicity, or withdrawal from the study for other reasons.
DRUG	Pazopanib 3 week	Pazopanib throughout each 3-week cycle as follows: 1) 200 mg twice weekly, 2) 200 mg every other day, 3) 200 mg qd, 4) 400 mg qd, 5) 800 mg qd, and 6) 1200 mg qd (Group 1). Maintenance pazopanib 800 mg qd for all 3 weeks throughout repeating 3-week cycles. Number of cycles: until death, loss of clinical benefit, unacceptable toxicity, or withdrawal from the study for other reasons.

Timeline

• Start date: 2009-11-18
• Primary completion: 2013-11-01
• Completion: 2013-11-01
• First posted: 2009-10-09
• Last updated: 2017-11-13

Locations

1 site across 1 country: United Kingdom