Trial Design:
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A phase 1/2 trial to assess the efficacy, safety and pharmacokinetic profile of three different dose schedules of SU11248 in patients with unresectable GIST who had failed or were intolerant of imatinib therapy. SU11248 doses of 25, 50, and 75 mg daily were administered at the following schedules:
- 25 mg/day, 2 weeks
on/2 weeks off
- 50 mg/day, 2 weeks
on/2 weeks off
- 75 mg/day, 2 weeks
on/2 weeks off
- 50 mg/day, 4 weeks
on/2 weeks off (schedule selected for continuation study)
- 50 mg/day, 2 weeks
on/1 weeks off
After 6 months, patients with continued clinical benefit were able to enter a continuation protocol to assess tumor progression and safety
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Objective:
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To establish one or more recommended phase 2 dose schedules for SU11248 based on safety, pharmacokinetics, and preclinical biological and clinical activity
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Number of Patients:
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- A total of 97
patients were enrolled in the initial trial
- Of these, 32 patients
(with partial response or stable disease for >6 months) were enrolled on the continuation protocol
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Key Inclusion Criteria:
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- Confirmed metastatic
or unresectable malignant GIST
- Treatment failure
with imatinib for any reason
- ECOG performance
score of 0 or 1
- Adequate organ
function
- Adequate nutritional
status
- Adequate coagulation
- Age ≥ 18 years
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Key Exclusion Criteria:
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- Patients who have not
recovered from the acute toxic effects of imatinib or other previous chemotherapy
- Any cytotoxic
chemotherapy of other anti-tumor therapy for GIST within 4 weeks of starting study medication
- Cardiovascular
disease within the 12 months prior to study drug administration
- Concurrent therapy
with medication known to have dysrhythmic potential
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Results:
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Efficacy-Initial Trial Results
CT Scan Response by RECIST |
Patients (n=97) (%) |
Complete response |
0 |
Partial response |
8 (8) |
Stable disease6 weeks-6 months ≥6 months |
32 (33) 36 (37) |
Stable disease <6 weeks or progressive disease |
21 (22) |
Median time to tumor progression was 8 months and median overall survival 20 months
Efficacy-Continuation Phase
Safety
- Most adverse events
were classed as grade 1 or 2 in severity
- Most commonly
reported grade 3 or 4 adverse events in the initial trial population were hypertension (17%), asymptomatic lipase increase (13%) and fatigue (10%)
- The adverse event
profile was similar in the continuation phase.
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Principal Investigator:
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Robert G. Maki, MD Memorial Hospital, New York
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SU11248 Product Information:
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SU11248 is now approved in many countries and is available as Sutent®.
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Trial results presented at the 2005 ASCO meeting: Abstract 9011. Maki RG, et al. Proc Am Soc Clin Oncol 2005. Abstract 9011.