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A Phase II Trial of TKI258 in Patients With Metastatic or Advanced Gastrointestinal Stromal Tumors (GIST) After Failure to Imatinib and Sunitinib(CTKI258AKR01T)

Phase 2
20 Years
Open (Enrolling)
Gastrointestinal Stromal Tumors

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Trial Information

A Phase II Trial of TKI258 in Patients With Metastatic or Advanced Gastrointestinal Stromal Tumors (GIST) After Failure to Imatinib and Sunitinib(CTKI258AKR01T)

It is well known that KIT and PDGFR which can be inhibited by TKI258 have a crucial role in
the development and proliferation of GIST, and in general FGFR has an important role in
angiogenesis and tumor proliferation in many cancers. We assume that TKI258 can be also
effective in patients with GIST. The objective of this study is to evaluate the safety and
activity of TKI258 given as salvage treatment for GIST after failure to standard imatinib
and sunitinib.

Inclusion Criteria

Inclusion criteria

- Age 20 years or older

- Histologically confirmed metastatic and/or advanced GIST with CD117(+), DOG-1(+), or
mutation in KIT or PDGFRα gene

- Failed (progressed and/or intolerable) after prior treatments for GIST, including at
least both imatinib and sunitinib .

- ECOG performance status of 0~2

- Resolution of all toxic effects of prior treatments to grade 0 or 1 by NCI-CTCAE
version 3.0

- At least one measurable lesion as defined by RECIST version 1.0.

- Adequate bone marrow, hepatic, renal, and other organ functions

- Neutrophil > 1,500/mm3

- Platelet > 75,000/mm3

- Hemoglobin > 8.0 g/dL

- Total bilirubin < 1.5 x upper limit of normal (ULN)

- AST/ALT < 2.5 x ULN (or < 5 x ULM in case of liver metastases)

- Creatinine < 1.5 x ULN

- Amylase, lipase < ULN

- Electrolytes should be within normal limits.

- Urine dipstick reading: Negative for proteinuria or, if documentation of +1 results
for protein on dipstick reading, then total urinary protein ≤ 500 mg and measured
creatinine clearance ≥ 50 mL/min/1.73m2 from a 24-hour urine collection

- Life expectancy > 12 weeks

- Women with reproductive potential must have a negative serum or urine pregnancy test

- Washout period of previous TKIs or chemotherapy for more than 4 times the half life.

- Provision of a signed written informed consent

Exclusion criteria

- Women of child-bearing potential who are pregnant or breast feeding or adults of
reproductive potential not employing an effective method of birth control.

- Clinically significant cardiac disease (New York Heart Association, Class III or IV)
or impaired cardiac function or clinically significant cardiac diseases,

- Uncontrolled infection.

- Diabetes mellitus (insulin dependent or independent disease, requiring chronic
medication) with signs of clinically significant peripheral vascular disease.

- Previous pericarditis; clinically significant pleural effusion in the previous months
or current ascites requiring two or more interventions/month.

- Known pre-existing clinically significant disorder of the hypothalamic-pituitary
axis, adrenal or thyroid glands.

- Prior acute or chronic pancreatitis of any etiology.

- Acute and chronic liver disease and all chronic liver impairment.

- Malabsorption syndrome or uncontrolled gastrointestinal toxicities with toxicity
greater than NCI CTCAE grade 2.

- Other severe, acute, or chronic medical or psychiatric condition or laboratory

- Treatment with any of the medications that have a potential risk of prolonging the QT
interval or inducing Torsades de Points and the treatment cannot be discontinued or
switched to a different medication prior to starting study drug.

- Use of ketoconazole, erythromycin, carbamazepine, phenobarbital, rifampin, phenytoin
and quinidine 2 weeks prior baseline.

- Major surgery ≤ 28 days prior to starting study drug or who have not recovered from
side effects of such therapy.

- Known diagnosis of HIV infection .

- History of another primary malignancy that is currently clinically significant or
currently requires active intervention.

- Patients with brain metastases as assessed by radiologic imaging

- Alcohol or substance abuse disorder.

- no other inhibitor of FGFR except sunitinib

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease control rate (DCR; response + stable disease)

Outcome Description:

evaluated with abdominal and pelvic dynamic CT scan every 4 weeks for the initial 8 weeks, and then every 8 weeks, using RECIST version 1.0

Outcome Time Frame:

Up to 24 weeks

Safety Issue:


Principal Investigator

Yoon-Koo Kang, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Asan Medical Center


Korea: Food and Drug Administration

Study ID:




Start Date:

September 2011

Completion Date:

March 2013

Related Keywords:

  • Gastrointestinal Stromal Tumors
  • This is a single-center
  • prospective
  • single-arm
  • open-label phase II study
  • Gastrointestinal Stromal Tumors