Trial Outcomes & Findings for Dovitinib for Imatinib/Sumitinib-failed Gastrointestinal Stromal Tumors (GIST): TKI258 (NCT NCT01440959)

Last Updated: 2020-01-18

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

Up to 24 weeks

Results posted on

2020-01-18

Participant Flow

Between September 2011 and April 2012, a total of 30 patients with metastatic and/or unresectable GISTs who had treatment failure with imatinib and sunitinib were enroled in Asan Medical Center, Seoul, Korea.

There are no specific approaches between enrollment and treatment.

Participant milestones

Participant milestones
Measure	TKI258 dovitinib : TKI258 at 500 mg/day on a 5 days on/2 days off dosing schedule
Overall Study STARTED	30
Overall Study COMPLETED	30
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Dovitinib for Imatinib/Sumitinib-failed Gastrointestinal Stromal Tumors (GIST): TKI258

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TKI258 n=30 Participants dovitinib : TKI258 at 500 mg/day on a 5 days on/2 days off dosing schedule
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	24 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants
Age, Continuous	56.5 years STANDARD_DEVIATION 10.4 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants
Region of Enrollment Korea, Republic of	30 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 24 weeks

Outcome measures

Outcome measures
Measure	TKI258 n=30 Participants dovitinib : TKI258 at 500 mg/day on a 5 days on/2 days off dosing schedule
Disease Control Rate (DCR; OR + Stable Disease)	13 Percentage of participants Interval 4.7 to 30.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	TKI258 n=30 Participants dovitinib : TKI258 at 500 mg/day on a 5 days on/2 days off dosing schedule
Overall Response Rate Using Both CT and PET Scans Response rate by CT	3 Percentage of participants
Overall Response Rate Using Both CT and PET Scans Response rate by PET	13 Percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	TKI258 n=30 Participants dovitinib : TKI258 at 500 mg/day on a 5 days on/2 days off dosing schedule
Number of Participants With Adverse Events	30 participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	TKI258 n=30 Participants dovitinib : TKI258 at 500 mg/day on a 5 days on/2 days off dosing schedule
Progression-free Survival	3.6 months Interval 3.5 to 3.7

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	TKI258 n=30 Participants dovitinib : TKI258 at 500 mg/day on a 5 days on/2 days off dosing schedule
Overall Survival	9.7 months Interval 6.0 to 13.4

Adverse Events

TKI258

Serious events: 8 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	TKI258 n=30 participants at risk dovitinib : TKI258 at 500 mg/day on a 5 days on/2 days off dosing schedule
Gastrointestinal disorders Anorexia	3.3% 1/30 • Up to 3 years
Cardiac disorders Left ventricular systolic dysfunction	3.3% 1/30 • Up to 3 years
Cardiac disorders QT prolongation	3.3% 1/30 • Up to 3 years
Cardiac disorders Plumonary thromboembolism	3.3% 1/30 • Up to 3 years
Blood and lymphatic system disorders Thrombocytopenia	6.7% 2/30 • Up to 3 years
Renal and urinary disorders Azotemia	3.3% 1/30 • Up to 3 years
Eye disorders Cataract	3.3% 1/30 • Up to 3 years

Other adverse events

Other adverse events
Measure	TKI258 n=30 participants at risk dovitinib : TKI258 at 500 mg/day on a 5 days on/2 days off dosing schedule
Blood and lymphatic system disorders Neutropenia	36.7% 11/30 • Up to 3 years
Blood and lymphatic system disorders Anemia	50.0% 15/30 • Up to 3 years
Blood and lymphatic system disorders Thrombocytopenia	43.3% 13/30 • Up to 3 years
Gastrointestinal disorders Anorexia	33.3% 10/30 • Up to 3 years
Gastrointestinal disorders Nausea	60.0% 18/30 • Up to 3 years
Gastrointestinal disorders Vomiting	40.0% 12/30 • Up to 3 years
Gastrointestinal disorders Dyspepsia	36.7% 11/30 • Up to 3 years
Gastrointestinal disorders Diarrhea	63.3% 19/30 • Up to 3 years
General disorders Asthenia	60.0% 18/30 • Up to 3 years
Cardiac disorders Hypertension	43.3% 13/30 • Up to 3 years
Renal and urinary disorders Proteinuria	33.3% 10/30 • Up to 3 years
Skin and subcutaneous tissue disorders Skin rash	30.0% 9/30 • Up to 3 years
Nervous system disorders Headache	20.0% 6/30 • Up to 3 years
Gastrointestinal disorders Abdominal pain	40.0% 12/30 • Up to 3 years
Renal and urinary disorders Azotemia	60.0% 18/30 • Up to 3 years
Hepatobiliary disorders Elevated aspartate aminotransferase	40.0% 12/30 • Up to 3 years
Hepatobiliary disorders Elevated alanine transaminase	46.7% 14/30 • Up to 3 years

Additional Information

Dr. Yoon-Koo Kang

Asan Medical Center

Phone: +82-2-3010-3210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place