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Gastrointestinal Stromal TumorsPhase 2NCT01440959

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

A Phase 2 study testing dovitinib in people with Gastrointestinal Stromal Tumors, run by Asan Medical Center at 1 site in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Gastrointestinal Stromal Tumors
What is being tested?
dovitinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteSouth Korea
Study dates
Sep 2011to Mar 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Asan Medical Center, University of Ulsan College of Medicine

    Seoul, 138-736

Other trials in South Korea

About this study

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)

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. .

Read the detailed description

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.

Being tested
dovitinib
Keywords
This is a single-center, prospective, single-arm, open-label phase II study
Medical subject headings
Gastrointestinal Stromal Tumors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • dovitinibDrug

    Also called A phase II study of TKI258

    TKI258 at 500 mg/day on a 5 days on/2 days off dosing schedule

Study groups in NCT01440959
Study groupRoleWhat they receive
TKI258ExperimentalNot described
Receives: Drug: dovitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease Control Rate (DCR; OR + Stable Disease)

    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.

    Measured: Up to 24 weeks

Secondary outcomes (6)

  1. Overall Response Rate Using Both CT and PET Scans

    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.

    Measured: Up to 24 weeks

  2. Efficacy According to the Primary Mutation Type

    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.

    Measured: Up to 24weeks

  3. Efficacy According to the Concentrations of Circulating Growth Factors

    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).

    Measured: Up to 24weeks

  4. Number of Participants With Adverse Events

    Adverse events will be graded according to Common Terminology Criteria for Adverse events version 3.0, up to 3 year.

    Measured: Monitoring of adverse events will be continued for at least 28 days following the last dose of study treatment, up to 3 year.

  5. Progression-free Survival

    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

    Measured: Up to 3 years

  6. Overall Survival

    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.

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2011 (estimated)
  2. Study startSep 2011
  3. Primary completionMar 2013
  4. Study completionMar 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01440959
Sponsor's protocol ID
AMC1403
Status last verified
Jan 2020
First submitted
8 Sep 2011
Last updated
18 Jan 2020
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing dovitinib in people with Gastrointestinal Stromal Tumors, run by Asan Medical Center at 1 site in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Mar 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Control Rate (DCR; OR + Stable Disease) (time frame: Up to 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01440959.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2020.

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