Results from a Continuation Trial of SU11248 in
Patients with Imatinib-resistant
Gastrointestinal Stromal Tumor (GIST)
View the ASCO presentation by Dr. Robert Maki
Trial results presented at the 2005 ASCO
meeting: Abstract 9011
Trial Design: |
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 |
Objective: |
To establish one or more
recommended phase 2 dose schedules for
SU11248 based on safety, pharmacokinetics,
and preclinical biological and clinical
activity |
Number of
Patients: |
- 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
|
Key Inclusion
Criteria: |
- 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
|
Key Exclusion
Criteria: |
- 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
|
Results: |
Efficacy-Initial Trial Results
|
CT
Scan Response by RECIST |
Patients
(n=97) (%) |
| Complete response |
0 |
| Partial response |
8
(8) |
Stable disease
6 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.
|
Principal
Investigator: |
Robert G. Maki, MD
Memorial Hospital, New York |
SU11248 Product
Information: |
SU11248 is now approved in many countries and is available as Sutent®. |
