Dovitinib for Imatinib/Sumitinib-failed Gastrointestinal Stromal Tumors (GIST): TKI258
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ClinicalTrials.gov Identifier: NCT01440959 |
Recruitment Status :
Completed
First Posted : September 27, 2011
Results First Posted : March 3, 2014
Last Update Posted : January 18, 2020
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Gastrointestinal Stromal Tumors | Drug: dovitinib | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 30 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase II Trial of TKI258 in Patients With Metastatic or Advanced Gastrointestinal Stromal Tumors (GIST) After Failure to Imatinib and Sunitinib(CTKI258AKR01T) |
Study Start Date : | September 2011 |
Actual Primary Completion Date : | March 2013 |
Actual Study Completion Date : | March 2013 |

Arm | Intervention/treatment |
---|---|
Experimental: TKI258 |
Drug: dovitinib
TKI258 at 500 mg/day on a 5 days on/2 days off dosing schedule
Other Name: A phase II study of TKI258 |
- Disease Control Rate (DCR; OR + Stable Disease) [ Time Frame: Up to 24 weeks ]
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.
- Overall Response Rate Using Both CT and PET Scans [ Time Frame: Up to 24 weeks ]PET scan will be performed at baseline and at 4 weeks of treatment. Metabolic response was defined based on the PET response criteria of the European Organization for Research and Treatment of Cancer (EORTC); a metabolic partial response (mPR) was defined as a 25% reduction in average SUVmax; metabolic stable disease (mSD) between a 25% decrease and 25% increase in average SUVmax; metabolic progressive disease (mPD) as a 25% increase in average SUVmax or the appearance of new uptake in metastatic lesions.
- Efficacy According to the Primary Mutation Type [ Time Frame: Up to 24weeks ]Correlation between efficacy results such as response, progression-free survival and overall survival, and primary mutation type including KIT exons 9, 11, 13, and 17 and PDGFRα exons 12 and 18.
- Efficacy According to the Concentrations of Circulating Growth Factors [ Time Frame: Up to 24weeks ]Correlation between efficacy results, such as response, progression-free survival, and overall survival andcirculating growth factors (including vascular endothelial growth factor, fibroblast growth factor, interleukin-8, placental growth factor, and fibroblast growth factor23), and soluble receptors (including soluble form of membrane bound vascular endothelial growth factor receptor-1 and -2).
- Number of Participants With Adverse Events [ Time Frame: Monitoring of adverse events will be continued for at least 28 days following the last dose of study treatment, up to 3 year. ]Adverse events will be graded according to Common Terminology Criteria for Adverse events version 3.0, up to 3 year.
- Progression-free Survival [ Time Frame: Up to 3 years ]
Progression-free survival is defined as the time from the first treatment to the onset of progressive disease per RECIST criteria or to the date of death whichever comes first. For patients who do not experience progressive disease or death, the progression-free survival duration will be right censored on the last disease assessment date.
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
- Overall Survival [ Time Frame: Up to 3 years ]Overall survival duration is calculated as time from the first treatment to the date of death. For patients who are still alive at the cut-off date for statistical reporting, the overall survival duration will be right censored on the last known alive date.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 20 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.
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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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01440959
Korea, Republic of | |
Asan Medical Center, University of Ulsan College of Medicine | |
Seoul,, Korea, Republic of, 138-736 |
Principal Investigator: | Yoon-Koo Kang, MD, PhD | Asan Medical Center |
Responsible Party: | Yoon-Koo Kang, Study Principal Investigator, Asan Medical Center |
ClinicalTrials.gov Identifier: | NCT01440959 |
Other Study ID Numbers: |
AMC1403 |
First Posted: | September 27, 2011 Key Record Dates |
Results First Posted: | March 3, 2014 |
Last Update Posted: | January 18, 2020 |
Last Verified: | January 2020 |
This is a single-center prospective single-arm open-label phase II study |
Gastrointestinal Stromal Tumors Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms |
Gastrointestinal Neoplasms Digestive System Neoplasms Digestive System Diseases Gastrointestinal Diseases |