A Phase II Study to Evaluate Efficacy and Safety of Dovitinib (TKI258) in Advanced Scirrhous Gastric Carcinoma Patients

Study Overview
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Brief Summary
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This is a prospective, open-label, single-arm, non-randomized, multi-center, phase II proof of concept (PoC) study with a two-stage design and Bayesian interim monitoring to evaluate efficacy and safety of single agent TKI258 in adult patients with scirrhous gastric carcinoma (SGC) that have progressed after one or two prior systemic treatments.

Official Title
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A Single-arm, Multi-center, Phase II Study to Evaluate Efficacy and Safety of Dovitinib (TKI258) in Adult Patients With Advanced Scirrhous Gastric Carcinoma That Have Progressed After One or Two Prior Systemic Treatments

Conditions
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Neoplasms, Adenocarcinoma, Scirrhous, Linitis Plastica, Stomach Neoplasms, Stomach Diseases, Neoplasms by Site

Intervention / Treatment
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* Drug: TKI258


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of advanced/metastatic scirrhous gastric carcinoma Evidence of diffusely infiltrating gastric lesions and/or at least one measurable extra-gastric lesion Patients previously treated with one or two systemic lines Documented radiological confirmation of disease progression ECOG performance status of 0 to 2 Male and female patients aged 20 years or greater Adequate liver, renal, and hematologic function Exclusion Criteria: Patients who received prior treatment with an FGFR inhibitor Patients with known brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases Patients with another primary malignancy within 3 years prior to starting study treatment Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TKI258<br>TKI258 is dosed on a flat scale of 500 mg, to be administered orally on a 5 days on / 2 days off dosing schedule which will be repeated every week. | Drug: TKI258<br>* TKI258 is dosed on a flat scale of 500 mg, to be administered orally on a 5 days on / 2 days off dosing schedule which will be repeated every week.<br>* Other names: Dovitinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease control rate (DCR) | Eight-week DCR is defined as the proportion of patients with best overall response of CR, PR or SD at the end of Week 8 as per local investigator's assessment. | up to 8 weeks after the start date of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to progression (TTP) | TTP is defined as the time from the start date of study treatment to the date of event defined as the first documented progression or death due to underlying cancer as per local investigator's assessment. | baseline and every 4 weeks until Week 17 and every 8 weeks after Week 17 until disease progression | 
| overall response rate (ORR) | ORR is defined as the proportion of patients with best overall response of CR or PR as per local investigator's assessment. | baseline and every 4 weeks until Week 17 and every 8 weeks after Week 17 until disease progress | 
| progression free survival (PFS) | PFS is defined as the time from the start date of study treatment to the date of event defined as the first documented progression or death due to any cause as per local investigator's assessment. | baseline and every 4 weeks until Week 17 and every 8 weeks after Week 17 until disease progress | 
| overall survival (OS) | OS is defined as the time from the start date of study treatment to the date of death from any cause. | every 8 weeks until death | 
| disease control rate (DCR) per independent central review | Eight-week DCR is as defined above. An independent central review of the radiological data will be performed and the results will be used for secondary supportive analyses. | up to 8 weeks after the start date of study treatment | 
| time to progression (TTP) per independent central review | TTP as defined above. An independent central review of the radiological data will be performed and the results will be used for secondary supportive analyses. | baseline and every 4 weeks until Week 17 and every 8 weeks after Week 17 until disease progress | 
| Safety and tolerability of TKI258 | Safety will be measured in terms of type, frequency and severity of adverse events according to CTCAE v4.03. | more than 30 days after the last date of study treatment | 
| Plasma concentrations of TKI258 | Pharmacokinetics (PK) of TKI258 at each scheduled time point of single dose and steady dose. | Week 1 Day 1 - Day 2: pre-dose (0 hour), 1, 2, 4, 6, 8, and 24 hour (pre-dose). and Week 4 Day 5 - Week 5 Day 1: pre-dose (0 hour), 1, 2, 4, 6, 8, 24, 48, and 72 hour (pre-dose) | 
| overall response rate (ORR) per independent central review | ORR as defined above. An independent central review of the radiological data will be performed and the results will be used for secondary supportive analyses. | baseline and every 4 weeks until Week 17 and every 8 weeks after Week 17 until disease progress | 
| progression free survival (PFS) per independent central review | PFS as defined above. An independent central review of the radiological data will be performed and the results will be used for secondary supportive analyses. | baseline and every 4 weeks until Week 17 and every 8 weeks after Week 17 until disease progress | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VEGF, FGFR, Neoplasms, Gastric Neoplasms, Cancer, Carcinoma, Gastric Diseases, Female Genital Diseases, Tumors, Oral Administration, Capsules, TKI258, TKI-258, TKI 258, Solid tumors, Advanced scirrhous gastric carcinoma, Gastric Cancer, Second-line or third-line treatment