NCT01089595

Trial of Tasigna (Nilotinib) 400 mg Twice Daily Alone or With Gleevec (Imatinib Mesylate) 400 mg Daily for Patients With Advanced Gastrointestinal Stromal Tumor (GIST)

Open Label Phase II Randomized Trial of Tasigna (Nilotinib) 400 mg Twice Daily Alone or in Combination With Gleevec (Imatinib Mesylate) 400 mg Daily for Patients With Advanced GIST That Have Progressed on High Dose Imatinib

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: Fox Chase Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Patients with advanced GIST are treated with imatinib. This study seeks to look at a new therapeutic agent at the time of tumor progression following treatment with 600-800 mg daily of imatinib. The study is looking to see if Nilotinib (tasigna) alone or in combination with imatinib (gleevec) is more effective at controlling disease.

Detailed description

Resistance to imatinib does develop and represents a major clinical challenge. Mechanisms implicated in imatinib resistance include: target resistance due to new KIT or PDGFRA mutations or over expression of the KIT protein; target modulation due to activation of an alternate receptor tyrosine kinase protein with loss of KIT oncoprotein expression; functional resistance due to KIT or PDGFRA activation without a secondary mutation; and alterations in imatinib uptake by P-glycoprotein. This study seeks to test nilotinib alone and nilotinib in combination with imatinib in patients that have progressed on imatinib. Nilotinib is a new synthetic second-generation inhibitor of the BCR-ABL tyrosine kinase that competes for the ATP-bindings sites of BCR-ABL. A completed phase I trial assessed the activity of nilotinib alone and in combination with imatinib in patients that have progressed on imatinib in a population of patients with imatinib refractory and intolerant patients. There were rare responses, but stable disease was observed in grater than 50% of patients. This study is aiming to treat patients with advanced or metastatic GIST who have disease progression on imatinib dose escalated up to 600 mg or greater. The rationale for exploring Nilotinib in this setting is to determine if it has therapeutic efficacy, with potentially less toxicity than the current standard of care for second line therapy. In addition, since it is not uncommon to see progression of some metastatic GIST lesions on imatinib, while others remain controlled, adding nilotinib may treat the progressing lesions while imatinib continues to control the areas without disease progression.

Conditions

• GIST
• Metastatic Disease

Interventions

Type	Name	Description
DRUG	Nilotinib	Nilotinib 400 mg po bid
DRUG	Nilotinib with Imatinib	Nilotinib 400 mg po BID Imatinib 400 mg po daily

Timeline

• Start date: 2009-02-01
• Primary completion: 2011-11-01
• Completion: 2012-03-01
• First posted: 2010-03-18
• Last updated: 2017-03-15
• Results posted: 2017-03-15

Locations

3 sites across 1 country: United States