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

Purpose

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


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Stomach Cancer Stomach Disorders

Genetic and Rare Diseases Information Center resources: Stomach Carcinoma

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

disease control rate (DCR) [ Time Frame: up to 8 weeks after the start date of study treatment ] [ Designated as safety issue: No ]
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) [ Time Frame: baseline and every 4 weeks until Week 17 and every 8 weeks after Week 17 until disease progression ] [ Designated as safety issue: No ]
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) [ Time Frame: baseline and every 4 weeks until Week 17 and every 8 weeks after Week 17 until disease progress ] [ Designated as safety issue: No ]
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) [ Time Frame: baseline and every 4 weeks until Week 17 and every 8 weeks after Week 17 until disease progress ] [ Designated as safety issue: No ]
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) [ Time Frame: every 8 weeks until death ] [ Designated as safety issue: No ]
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 [ Time Frame: up to 8 weeks after the start date of study treatment ] [ Designated as safety issue: No ]
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 [ Time Frame: baseline and every 4 weeks until Week 17 and every 8 weeks after Week 17 until disease progress ] [ Designated as safety issue: No ]
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 [ Time Frame: more than 30 days after the last date of study treatment ] [ Designated as safety issue: Yes ]
Safety will be measured in terms of type, frequency and severity of adverse events according to CTCAE v4.03.
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) ] [ Designated as safety issue: No ]
Pharmacokinetics (PK) of TKI258 at each scheduled time point of single dose and steady dose.
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 ] [ Designated as safety issue: No ]
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 [ Time Frame: baseline and every 4 weeks until Week 17 and every 8 weeks after Week 17 until disease progress ] [ Designated as safety issue: No ]
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.


Enrollment:	11
Study Start Date:	June 2012
Study Completion Date:	September 2013
Primary Completion Date:	September 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility


Ages Eligible for Study:	20 Years and older
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01576380

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

No publications provided


Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01576380 History of Changes
Other Study ID Numbers:	CTKI258A1201
Study First Received:	April 2, 2012
Last Updated:	June 4, 2014
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by Novartis:


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:


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

ClinicalTrials.gov processed this record on March 02, 2015