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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TKI258 | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TKI258 | Drug | 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. |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Nagoya | Aichi-ken | 464-8681 | Japan | ||
| Novartis Investigative Site |
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|
| 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 |
| Kashiwa |
| Chiba |
| 277-8577 |
| Japan |
| Novartis Investigative Site | Matsuyama | Ehime | 791-0280 | Japan |
| Novartis Investigative Site | Sapporo | Hokkaido | 060-8648 | Japan |
| Novartis Investigative Site | Takatsuki | Osaka | 569-8686 | Japan |
| Novartis Investigative Site | Sunto-gun | Shizuoka | 411-8777 | Japan |
| Novartis Investigative Site | Chuo-ku | Tokyo | 104-0045 | Japan |
| Novartis Investigative Site | Koto | Tokyo | 135-8550 | Japan |
| ID | Term |
|---|---|
| D002293 | Adenocarcinoma, Scirrhous |
| D008039 | Linitis Plastica |
| D013274 | Stomach Neoplasms |
| D013272 | Stomach Diseases |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D002277 | Carcinoma |
| D005831 | Genital Diseases, Female |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
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| ID | Term |
|---|---|
| C500007 | 4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one |
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