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Gastrointestinal Stromal TumorsPhase 1NCT02268435

Dovitinib in Combination With Imatinib in Patients With Gastrointestinal Stromal Tumors

A Phase 1 study testing dovitinib plus imatinib in people with Gastrointestinal Stromal Tumors, run by Asan Medical Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The objective of this study is to determine the recommended dose of combination of dovitinib and imatinib in phase I study. Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Gastrointestinal Stromal Tumors
What is being tested?
dovitinib plus imatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Mar 2015to Nov 2016
Phase
Phase 1
Are there results?
None posted in the registry

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

Who may be able to join

  • Age 19 years or older
  • Histologically confirmed metastatic or unresectable GIST with CD117(+), DOG-1(+), or mutation in KIT or PDGFRα gene
  • Disease control (response or stabilization for at least 6 months with first-line imatinib and failure of prior treatments for GIST, including at least both imatinib and sunitinib and/or regorafenib. However, patients with imatinib rechallenge will not be accrued.
  • ECOG performance status of 0~2
  • Resolution of all toxic effects of prior treatments to grade 0 or 1
  • At least one evaluable or measurable lesion for phase I study
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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
  • AST/ALT < 2.5 x ULN with no exceptions
  • Creatinine < 1.5 x ULN
  • Life expectancy > 12 weeks
  • Women with reproductive potential must have a negative serum or urine pregnancy test; and men and women of reproductive potential must practice an effective method of avoiding pregnancy while receiving study drug.
  • Washout period of previous TKIs or chemotherapy for more than 4 times the half life.
  • No prior use of dovitinib or other inhibitors of FGFR except regorafenib
  • 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. Barrier contraceptives must be used throughout the trial in both sexes.
  • Clinically significant cardiac disease or impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
  • LVEF < 45%
  • Complete left bundle branch block
  • Obligate use of a cardiac pacemaker
  • Congenital long QT syndrome
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  • History or presence of ventricular tachyarrhythmia
  • Presence of unstable atrial fibrillation .
  • Clinically significant resting bradycardia
  • Uncontrolled hypertension
  • QTc > 480 msec on screening ECG
  • Right bundle branch block + left anterior hemiblock
  • Angina pectoris ≤ 3 months prior to starting study drug
  • Acute Myocardial Infarction ≤ 3 months prior to starting study drug
  • Other clinically significant heart disease
  • Uncontrolled infection
  • Subjects who did not tolerate previous imatinib treatment.
  • Diabetes mellitus with signs of clinically significant peripheral vascular disease
  • Previous pericarditis; clinically significant pleural effusion in the previous 12 months or current ascites requiring two or more interventions/month 7. Known pre-existing clinically significant disorder of the hypothalamic-pituitary axis, adrenal or thyroid glands
  • 8. Prior acute or chronic pancreatitis of any etiology 9. Malabsorption syndrome or uncontrolled gastrointestinal toxicities with toxicity greater than NCI CTCAE grade 2 10. Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for this study 11. 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 12. Use of ketoconazole, erythromycin, carbamazepine, phenobarbital, rifampin, phenytoin and quinidine 2 weeks prior baseline 13. Major surgery ≤ 28 days prior to starting study drug or who have not recovered from side effects of such therapy 14. Known diagnosis of HIV infection 15. History of another primary malignancy that is currently clinically significant or currently requires active intervention 16. Patients with brain metastases as assessed by radiologic imaging due to symptoms clinically suspected of brain metastases 17. Alcohol or substance abuse disorder

About this study

Official title: A Trial of Dovitinib in Combination With Imatinib in Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumors After Failure to Imatinib and Sunitinib

The objective of this study is to determine the recommended dose of combination of dovitinib and imatinib in phase I study.

Read the detailed description

combination of dovitinib and imatinib could lead to additive or synergistic effect in patients who had failure of standard TKI therapies including imatinib, sunitinib, and/or regorafenib. In this phase I-II study of dovitinib plus imatinib, we aim to determine a recommended dose of dovitinib plus imatinib and to evaluate the safety and activity of the combination at the recommended dose as a 3rd or more line of treatment in metastatic or unresectable GIST.

Being tested
dovitinib plus imatinib
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.

  • dovitinib plus imatinibDrug

    Dovitinib once daily on a 5 days on/2 days off dosing schedule, and imatinib once daily on a continuous dosing schedule

Study groups in NCT02268435
Study groupRoleWhat they receive
Dovitinib plus ImatinibExperimentalDovitinib once daily on a 5 days on/2 days off dosing schedule, and imatinib once daily on a continuous dosing schedule
Receives: Drug: dovitinib plus imatinib

What is being measured

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

  1. Maximal tolerated dose and recommended dose

    Initially three patients will be treated at each dose level. If one out of three patients experiences a DLT, three additional patients will be entered at that dose level. Dose escalation will be continued until DLTs are experienced in two or more out of six patients (more than 33% of patient cohort), which will be defined as the MTD.If more than 33% of patients experience a DLT in a dose level, one doe level below will be the RD

    Measured: 3 years

Secondary outcomes (9)

  1. Disease control rate

    response + stable disease evaluated with abdominal and pelvic spiral CT scan every 4 weeks for the first 8 weeks, and then every 8 weeks, using RECIST criteria v1.1

    Measured: 3 years

  2. Overall response rate

    response + stable disease evaluated with abdominal and pelvic spiral CT scan every 4 weeks for the first 8 weeks, and then every 8 weeks, using RECIST criteria v1.1

    Measured: 3 years

  3. Number of Participants with Adverse Events as a Measure of Safety

    Safety by NCI CTCAE version 4.0

    Measured: 3 years

  4. Progression-free survival

    response + stable disease evaluated with abdominal and pelvic spiral CT scan every 4 weeks for the first 8 weeks, and then every 8 weeks, using RECIST criteria v1.1

    Measured: 3 years

  5. Overall survival (OS)

    OS assessment dates will be the time point when 6 months have passed after the enrollment of the last patient

    Measured: 3 years

  6. optionally, correlation of efficacy with potential biomarkers

    mutational analysis of KIT exons 9, 11, 13, and 17, and PDGFRα exons 12, 14, and 18 with direct sequencing using DNA extracted from archival tissues and/or newly obtained tissues at baseline, and with BEAMing assay using ctDNA extracted from plasma at baseline and every time when follow-up CT scans are conducted; optionally circulating growth factors including but not limited to VEGF, bFGF, IL-8, PLGF, FGFR2, and FGF23, and soluble receptors including but not limited to sVEGFR1 and 2 with plasma collected at baseline and on Cycle 1 Week 4 Day 5

    Measured: 3 years

  7. next generation sequencing will be performed in newly obtained tissues at baseline to find out new genetic changes after failure of previous standard TKIs

    Measured: 3 years

  8. Optionally, activation of FGFR signaling will be analyzed using the reverse phase protein microarray and/or immunohistochemistry including but not limited to pFRS2 and pFGFR in archival tissues and/or newly obtained tissues at baseline

    Measured: 3 years

  9. Imatinib and dovitinib plasma concentrations vs time profile, and basic pharmacokinetics parameters

    PK samples will be taken at 0 hour (pre-dose) and at 1, 2, 3, 4, 6, and 8 hours (post-dose) after administration of dovitinib and imatinib on Cycle 1 Week 1 Day 1, Cycle 1 Week 1 Day 5, and Cycle 1 Week 4 Day 5

    Measured: 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 posted20 Oct 2014 (estimated)
  2. Study startMar 2015
  3. Primary completionAug 2016 (estimated)
  4. Study completionNov 2016 (estimated)

Why it stopped: Dovitinib Production stopped

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02268435
Sponsor's protocol ID
AMC1401
Status last verified
Aug 2015
First submitted
7 Oct 2014
Last updated
4 Aug 2015
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing dovitinib plus imatinib in people with Gastrointestinal Stromal Tumors, run by Asan Medical Center.

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 18 inclusion and 20 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: withdrawn, as of the sponsor's last update on 4 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.

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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Maximal tolerated dose and recommended dose (time frame: 3 years). 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 NCT02268435.

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 4 Aug 2015.

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