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)
|GIST Metastatic Disease||Drug: Nilotinib Drug: Nilotinib with Imatinib||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||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|
- Progression Free Survival [ Time Frame: 6 months until death or for 5 years ]Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression. It will be determined for both RECIST (Response Evaluation Criteria in Solid Tumors) and CHOI criteria.
- Best Overall Response Using Response Evaluation Criteria in Solid Tumors, Choi Criteria, and Positron Emission Tomography Imaging [ Time Frame: Every 8 weeks for up to 5 years ]
|Study Start Date:||February 2009|
|Study Completion Date:||March 2012|
|Primary Completion Date:||November 2011 (Final data collection date for primary outcome measure)|
Active Comparator: Nilotinib
Nilotinib 400 mg po bid
Nilotinib 400 mg po bid
Other Name: Tasigna
Active Comparator: Nilotinib + Imatinib
Nilotinib 400 mg BID with Imatinib 400 mg daily
Drug: Nilotinib with Imatinib
Nilotinib 400 mg po BID Imatinib 400 mg po daily
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01089595
|United States, Missouri|
|Siteman Cancer Center, Washington University School of Mediciine|
|St Louis, Missouri, United States, 63110|
|United States, North Carolina|
|Wake Forest University|
|Winston-Salem, North Carolina, United States, 27157-1082|
|United States, Pennsylvania|
|Fox Chase Cancer Center|
|Philadelphia, Pennsylvania, United States, 19111|
|Principal Investigator:||Margaret von Mehren, MD||Fox Chase Cancer Center|