Adenocarcinoma, Scirrhous, Linitis Plastica, Neoplasms, Neoplasms by Site, Stomach Diseases, Stomach Neoplasms
Conditions
Keywords
Solid tumors, Advanced scirrhous gastric carcinoma, Gastric Cancer, Second-line or third-line treatment, VEGF, FGFR, Neoplasms, Gastric Neoplasms, Cancer, Carcinoma, Gastric Diseases, Female Genital Diseases, Tumors, Oral Administration, Capsules, TKI258, TKI-258, TKI 258
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.
Interventions
DRUGTKI258
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.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Japan
Outcome results
None listed