Results from a Continuation Trial of SU11248 in Patients with Imatinib-Resistant Gastrointestinal Stromal Tumor (GIST)

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:

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:

SU11248 Product
Information:

SU11248 is now approved in many countries and is available as Sutent®.