Een gerandomiseerde, open-label, multicenter studie om de effectiviteit van nilotinib te vergelijken met de beste ondersteunende behandeling met of zonder een tyrosine kinase remmer (keus van de onderzoeker) bij volwassen patiënten met gastrointestinale stromacel tumoren die resistent zijn voor zowel imatinib en sunitinib.

Nilotinib is a second generation inhibitor of the Bcr-Abl tyrosine kinase
which, like imatinib. Nilotinib also inhibits the stem cell factor receptor
c-Kit tyrosine kinase, which is often associated with gastrointestinal stromal
tumors (GIST).

In this study, as of 15 August, 2006, 53 patients (48 imatinib-resistant and 5
imatinib-intolerant) were enrolled. 18 patients received nilotinib alone (400
mg bid), 19 patients escalating doses of nilotinib (200 mg qd, 400 mg qd, or
400 mg bid) in combination with imatinib (400 mg bid), and 16 patients
nilotinib 400 mg bid plus imatinib 400 mg for 8 to 337 days (median 113 days).
The median duration of treatment in patients who received nilotinib alone was
186 days (8-337 days).
39 patients had prior failure of second-line therapies in addition to
progression on imatinib. Thirteen of the 18 patients treated with nilotinib
alone had failed other therapies in addition to imatinib, including sunitinib,
AMG-706, RAD-001or dasatinib.
Of the 18 patients who received nilotinib alone one patient achieved a partial
response lasting approximately 6 months and thirteen patients exhibited disease
stabilization. The median duration of response, including stable disease, was
5.3 months. The estimated median progression free survival (PFS) was
approximately 6 months
.

Primary
* To evaluate whether the efficacy of nilotinib is superior to the control arm
(as measured by progression free survival
Secondary
* To compare the response rate, and time to response, duration of response, and
time to tumor progression of nilotinib with the control arm
* To compare overall survival of nilotinib with the control arm
* To assess the safety and tolerability of nilotinib as measured by rate and
severity of adverse events.

Changed in Amendment 1 into:
This is a randomized, open-label, parallel group, two-arm study with an
Extension study. At Day 1 patients will be randomized in a 2:1 ratio to
nilotinib 400 mg bid arm or the control arm. The control arm includes the
following three options:
Best supportive care or best supportive care plus imatinib or sunitinib at last
tolerated dose.
The choice of one of these options will be at the investigator*s discretion and
patients will not be permitted to switch treatment within this arm.

Amendment 1

Arm 1:
2 x daily 400 mg nilotinib (AMN107)

Arm 2 (control arm):
The control arm includes the following three options:
Best supportive care OR
Best supportive care plus imatinib OR
Best supportive care plus sunitinib
The choice of one of these options will be at the investigator*s discretion and
patients will not be permitted to switch treatment within this arm.

Toxicity of nilotinib, or imatinib or sunitinib depending on the treatment arm.
Radiation exposure of PET and CT-scan and/or an allergic reaction on the
contrast fluid.
When a biopsy is done, bleeding and pain. The risk of taking blood may include
pain, faint and/or bruisin.