Gastric Cancer
Conditions
Keywords
Gastric Cancer, Dovitinib
Brief summary
This is a single-center, prospective, single-arm, open-label phase II study
Detailed description
In this study, we will evaluate the efficacy and safety of TKI258(Dovitinib) monotherapy as a salvage chemotherapy after failure of standard first or second-line chemotherapy in metastatic or unresectable gastric cancer harboring FGFR2 amplification.
Interventions
DRUGDovitinib
* Study treatment: TKI258 single agent on a 5 days-on/2 days-off schedule * Study drug: TKI258 capsule * Dose: 500mg p.o. qd * Every 3 weeks
Sponsors
Novartis
Asan Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically proven metastatic or unresectable adenocarcinoma of stomach or gastroesophageal junction * Patients with progressive disease (radiological confirmation required) after one or two lines of chemotherapy in palliative setting for advanced gastric cancer. Adjuvant or neoadjuvant chemotherapy is not counted as one line of prior chemotherapy. * FGFR2 amplification (copy number \> 3, identified by real time PCR using TaqMan probe) by prescreening or screening procedure. Prescreening can be performed with Real Time PCR for FGFR2 amplification any time during the prior chemotherapy. At least 18 patients should have 6 or more copy numbers of FGFR2 (see Statistical Methods and Data Analysis). * Presence of at least one measurable disease (for co-primary endpoint of overall response rate in patients with FGFR2 copy number \> 6) or one evaluable disease (for co-primary endpoint of PFS in patients with FGFR2 copy number \> 3) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 * Age of 18 years or older * Expected life expectancy of more than 3 months * ECOG performance status 0\ 2 * Resolution of all toxic effects of prior treatments to grade 0 or 1 by NCI-CTCAE version 4.0 * 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) * 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 chemotherapy for more than 4 times the half life or at least 2 weeks after completion of prior chemotherapy whichever comes first * No prior FGF/FGFR inhibitor * No prior radiation therapy within 2 weeks of the study (Irradiated lesions should not be included in the evaluable lesions.) * Written informed consent
Exclusion criteria
* Past or concurrent history of neoplasm other than gastric adenocarcinoma, except for curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix uteri * Bowel obstruction * Evidence of serious gastrointestinal bleeding * 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. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test 72 hours prior to starting TKI258. * Clinically significant cardiac disease (New York Heart Association, Class III or IV) or impaired cardiac function or clinically significant cardiac diseases, including any one of the following: (LVEF \< 45% as determined by MUGA scan or echocardiogram, 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 (ventricular response \> 100 bpm). Patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| response rate | 1year | To evaluate with abdominal and pelvic dynamic CT scan every 6 weeks using RECIST version 1.1 |
| Progression-free survival | From date of enrollment to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years | To evaluate progression-free survival (PFS) with TKI258(Dovitinib) administered orally at 500 mg/day on a 5 days on/2 days off dosing schedule to adult patients \> 18 years with evaluable metastatic or unresectable gastric cancer harboring FGFR2 amplification (copy number \> 3, identified by real time PCR using TaqMan probe) who failed one or two lines of chemotherapy in palliative setting. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events | 1year | Monitoring for safety and toxicity will be performed every cycle (3 weeks) of chemotherapy and whenever patients have problems. |
| Evaluation of Efficacy | From date of randomization to death from any cause, assessed up to 2 years | To correlate concentrations of circulating growth factors, soluble receptors with efficacy (response rate, progression free survival, and overall survival) of TKI258 at 500 mg/day on a 5 days on/2 days off dosing schedule. |
| FGFR2 copy number | 1year | To compare FGFR2 copy number determined by FISH(fluorescence in situ hybridization) with FGFR2 copy number identified by real time PCR using TaqMan Probe. |
Countries
South Korea
Outcome results
None listed