Clinical trial · Interventional
Dovitinib for Imatinib/Sumitinib-failed Gastrointestinal Stromal Tumors (GIST): TKI258
A Phase II Trial of TKI258 in Patients With Metastatic or Advanced Gastrointestinal Stromal Tumors (GIST) After Failure to Imatinib and Sunitinib(CTKI258AKR01T)
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
With discovery of KIT mutations and the advent of KIT tyrosine kinase inhibitor imatinib (GlivecTM, Novartis), there has been substantial improvement in overall survival in patients with advanced and/or metastatic gastrointestinal tumors (GIST). Recently, sunitinib (SuteneTM, Pfizer) showed activity as second-line therapy in GIST patients after failure with imatinib. However, virtually all patients will eventually progress or become intolerable after the first-line imatinib and the second-line sunitinib. Dovitinib (TKI258, Novartis) is a multi-kinase inhibitor. TKI258 is a potent inhibitor of the VEGFR 1, 2, and 3, FGFR1, 2 and 3, PDGFRβ, Kit, RET, TrkA, CSF 1R, and FLT3 with inhibitory concentration 50% (IC50s) of less than 40nM. Stem cell factor (SCF) also termed KIT ligand, or steel factor has been shown to modulate tumor angiogenesis. In cultured human endothelial cells and Kit expressing cancer cells, TKI258 inhibits VEGF- and SCF-stimulated mitogenesis. .
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Gastrointestinal Stromal Tumors | Gastrointestinal Stromal Tumor | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| dovitinib | Drug | Dovitinib | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- TKI258
- interventionNames
- Drug: dovitinib
Primary outcomes (1)
- measure
- Disease Control Rate (DCR; OR + Stable Disease)
- timeFrame
- Up to 24 weeks
- description
- Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR; Progressive disease (PD), \>20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), Insufficient change to qualify for PR or PD This was evaluated with abdominal and pelvic dynamic CT scan every 4 weeks for the initial 8 weeks, and then every 8 weeks.
Secondary outcomes (6)
- measure
- Overall Response Rate Using Both CT and PET Scans
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 20 Years
Show eligibility criteria text
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 abnormality. * 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
References
Publications (0)
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