A Phase II Study to Evaluate Efficacy and Safety of Dovitinib (TKI258) in Advanced Scirrhous Gastric Carcinoma Patients
- Conditions
- Linitis PlasticaStomach DiseasesNeoplasmsAdenocarcinoma, ScirrhousStomach NeoplasmsNeoplasms by Site
- Interventions
- Registration Number
- NCT01576380
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 11
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description TKI258 TKI258 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.
- Primary Outcome Measures
Name Time Method disease control rate (DCR) up to 8 weeks after the start date of study treatment 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.
- Secondary Outcome Measures
Name Time Method progression free survival (PFS) baseline and every 4 weeks until Week 17 and every 8 weeks after Week 17 until disease progress 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.
Plasma concentrations of TKI258 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) Pharmacokinetics (PK) of TKI258 at each scheduled time point of single dose and steady dose.
time to progression (TTP) baseline and every 4 weeks until Week 17 and every 8 weeks after Week 17 until disease progression 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.
time to progression (TTP) per independent central review baseline and every 4 weeks until Week 17 and every 8 weeks after Week 17 until disease progress 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.
Safety and tolerability of TKI258 more than 30 days after the last date of study treatment Safety will be measured in terms of type, frequency and severity of adverse events according to CTCAE v4.03.
overall response rate (ORR) baseline and every 4 weeks until Week 17 and every 8 weeks after Week 17 until disease progress ORR is defined as the proportion of patients with best overall response of CR or PR as per local investigator's assessment.
progression free survival (PFS) per independent central review baseline and every 4 weeks until Week 17 and every 8 weeks after Week 17 until disease progress 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.
overall survival (OS) every 8 weeks until death OS is defined as the time from the start date of study treatment to the date of death from any cause.
disease control rate (DCR) per independent central review up to 8 weeks after the start date of study treatment 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.
overall response rate (ORR) per independent central review baseline and every 4 weeks until Week 17 and every 8 weeks after Week 17 until disease progress 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.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇯🇵Koto, Tokyo, Japan