Dovitinib in Combination With Imatinib in Patients With Gastrointestinal Stromal Tumors

NCT02268435 | Withdrawn Phase 1

• 1 other identifier: AMC1401
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Gastrointestinal Stromal Tumors

Outcome Measures

Primary Outcomes (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

  3 years

Secondary Outcomes (9)

• Disease control rate

  3 years

• Overall response rate

  3 years

• Number of Participants with Adverse Events as a Measure of Safety

  3 years

• Progression-free survival

  3 years

• Overall survival (OS)

  3 years

Study Arms (1)

Dovitinib plus Imatinib

EXPERIMENTAL

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

Drug: dovitinib plus imatinib

Interventions

dovitinib plus imatinib DRUG

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

Dovitinib plus Imatinib

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Asan Medical Center: lead

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Yoon-Koo Kang, PhD

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 7, 2014
• First Posted: October 20, 2014
• Study Start: March 1, 2015
• Primary Completion: August 1, 2016
• Study Completion: November 1, 2016
• Last Updated: August 4, 2015

Record last verified: 2015-08