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

Study Description

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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
Adenocarcinoma, Scirrhous; Linitis Plastica; Stomach Neoplasms; Stomach Diseases; Neoplasms by Site; Neoplasms	Drug: TKI258	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	11 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	June 2012
Actual Primary Completion Date :	September 2013
Actual Study Completion Date :	September 2013

Arms and Interventions

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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 Name: Dovitinib

Outcome Measures

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Primary Outcome Measures :

1. disease control rate (DCR) [ Time Frame: 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 :

1. time to progression (TTP) [ Time Frame: 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.
2. overall response rate (ORR) [ Time Frame: 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.
3. progression free survival (PFS) [ Time Frame: 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.
4. overall survival (OS) [ Time Frame: 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.
5. disease control rate (DCR) per independent central review [ Time Frame: 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.
6. time to progression (TTP) per independent central review [ Time Frame: 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.
7. Safety and tolerability of TKI258 [ Time Frame: 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.
8. Plasma concentrations of TKI258 [ Time Frame: 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.
9. overall response rate (ORR) per independent central review [ Time Frame: 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.
10. progression free survival (PFS) per independent central review [ Time Frame: 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

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Ages Eligible for Study:	20 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

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Locations

Japan
Novartis Investigative Site
Nagoya, Aichi, Japan, 464-8681
Novartis Investigative Site
Kashiwa, Chiba, Japan, 277-8577
Novartis Investigative Site
Matsuyama, Ehime, Japan, 791-0280
Novartis Investigative Site
Sapporo-city, Hokkaido, Japan, 060-8648
Novartis Investigative Site
Takatsuki, Osaka, Japan, 569-8686
Novartis Investigative Site
Sunto-gun, Shizuoka, Japan, 411-8777
Novartis Investigative Site
Chuo-ku, Tokyo, Japan, 104-0045
Novartis Investigative Site
Koto, Tokyo, Japan, 135-8550

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information

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Additional Information:

Results for CTKI258A1201 from the Novartis Clinical Trials website 

Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01576380 History of Changes
Other Study ID Numbers:	CTKI258A1201
First Posted:	April 12, 2012
Last Update Posted:	February 27, 2017
Last Verified:	February 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

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

Additional relevant MeSH terms:

Carcinoma; Neoplasms; Adenocarcinoma; Stomach Neoplasms; Neoplasms by Site; Stomach Diseases; Linitis Plastica	Adenocarcinoma, Scirrhous; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases