A Phase II Study to Evaluate Efficacy and Safety of Dovitinib (TKI258) in Advanced Scirrhous Gastric Carcinoma Patients
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: 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.
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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) 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.
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Nagoya | Aichi | Japan | 464-8681 |
| 2 | Novartis Investigative Site | Kashiwa | Chiba | Japan | 277-8577 |
| 3 | Novartis Investigative Site | Matsuyama | Ehime | Japan | 791-0280 |
| 4 | Novartis Investigative Site | Sapporo-city | Hokkaido | Japan | 060-8648 |
| 5 | Novartis Investigative Site | Takatsuki | Osaka | Japan | 569-8686 |
| 6 | Novartis Investigative Site | Sunto-gun | Shizuoka | Japan | 411-8777 |
| 7 | Novartis Investigative Site | Chuo-ku | Tokyo | Japan | 104-0045 |
| 8 | Novartis Investigative Site | Koto | Tokyo | Japan | 135-8550 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CTKI258A1201