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 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.
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®.

Trial results presented at the 2005 ASCO meeting: Abstract 9011. Maki RG, et al. Proc Am Soc Clin Oncol 2005. Abstract 9011.