Study of GSK1363089 in Metastatic Gastric Cancer

Neoplasms, Gastrointestinal Tract Clinical Trial

Official title:

A Phase 2 Study of GSK1363089 (XL880) Administered Orally to Subjects With Metastatic Gastric Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00725712
• Other study ID #: MET111643
• Status: Completed
• Phase: Phase 2
• First received: July 29, 2008
• Last updated: October 11, 2016
• Start date: March 2007
• Est. completion date: November 2009

Study information

• Verified date: October 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This clinical study is being conducted at multiple sites to determine the best confirmed response rate, safety, and tolerability of GSK1363089 treatment in metastatic gastric carcinoma.

Other known NCT identifiers

• NCT00415480

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• histologically confirmed diagnosis of advanced or metastatic gastric carcinoma, or adenocarcinoma of the gastroesophageal junction or of the distal esophagus. Subjects with tumors of the gastroesophageal junction or of the distal esophagus may be eligible provided that the tumor is not of squamous or sarcomatous histology

• Measurable disease

• The subject consents to provide paired tumor biopsies, directly prior to commencing study treatment and then between Days 5 and 8.

• The subject has an ECOG performance status =2.

• The subject is able to ingest the GSK1363089 capsules.

• In the adrenocorticotropic hormone (ACTH) stimulation test, the subject has a serum cortisol level =20 µg/dL (552 nmol/L) 30-90 minutes after injection of ACTH.

• The subject has liver, kidney and marrow function.

• The subject is capable of understanding and complying with the protocol and has signed the informed consent document.

• Sexually active subjects (male and female) must use a medically-accepted method of contraception during the course of the study.

• Female subjects of childbearing potential must have a negative serum pregnancy test at screening.

• The subject has had no other diagnosis of malignancy (unless non-melanoma skin cancer or a malignancy diagnosed =5 years ago, and has no evidence of disease for 5 years prior to the screening for this study).

• QTc < 470 msec.

Exclusion Criteria:

• The subject has received more than two lines of prior cytotoxic chemotherapy for locally advanced or metastatic disease. For the purpose of this protocol, neoadjuvant therapy would not be considered to be prior cytotoxic chemotherapy. In addition, potential subjects who have received prior treatment with c-MET signaling inhibitor are excluded.

• The subject has received an investigational drug within 14 days of the first dose of study drug.

• The subject has received chemotherapy, immunotherapy, or radiation therapy (to

=25% of his or her bone marrow) within 14 days or has received nitrosoureas or mitomycin C within 6 weeks prior to the scheduled first dose of GSK1363089.

• The subject has AEs due to investigational drugs or other medications administered more than 21 days prior to enrollment that have not recovered to Grade =1 using NCI CTCAE v3.0, with the exception of alopecia greater than grade 1.

• The subject has known brain metastases.

• The subject has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• The subject is pregnant or breastfeeding.

• The subject is known to be positive for the human immunodeficiency virus (HIV).

• The subject has a previously identified allergy or hypersensitivity to components of the GSK1363089 formulation.

• The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Digestive System Neoplasms
• Gastrointestinal Neoplasms
• Neoplasms, Gastrointestinal Tract
• Stomach Neoplasms

Intervention

Drug:
• GSK1363089 (formerly XL880)
c-MET tyrosine kinase inhibitor

Locations

Country	Name	City	State
United States	GSK Investigational Site	Albuquerque	New Mexico
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Billings	Montana
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Detroit	Michigan
United States	GSK Investigational Site	Durham	North Carolina
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Madison	Wisconsin
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Scottsdale	Arizona
United States	GSK Investigational Site	Stanford	California
United States	GSK Investigational Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

References & Publications (3)

Jhawer M, Kindler HL, Wainberg Z, Ford J, Kunz P, Tang L, McCallum S, Kallender H, Shah MA Assessment of two dosing schedules of GSK1363089 (GSK089), a dual MET/VEGFR2 inhibitor, in metastatic gastric cancern (GC): Interim results of a multicenter phase I

Jhawer MP, Kindler HL, Wainberg ZA, Hecht JR, Kerr RO, Ford JM, Henderson C, Mueller T, Keer HN, Shah MA Preliminary activity of XL880, a dual MET/VEGFR2 inhibitor, in MET amplified poorly differentiated gastric cancer (PDGC): Interim results of a multice

Shah MA, Wainberg ZA, Catenacci DV, Hochster HS, Ford J, Kunz P, Lee FC, Kallender H, Cecchi F, Rabe DC, Keer H, Martin AM, Liu Y, Gagnon R, Bonate P, Liu L, Gilmer T, Bottaro DP. Phase II study evaluating 2 dosing schedules of oral foretinib (GSK1363089), cMET/VEGFR2 inhibitor, in patients with metastatic gastric cancer. PLoS One. 2013;8(3):e54014. doi: 10.1371/journal.pone.0054014. Epub 2013 Mar 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (RECIST) of GSK1363089 on 2 different dosing regimens		4 months (average)	No
Primary	Number of subjects with adverse events, and clinically significant changes in vital signs and laboratory values		4 months (average)	No
Secondary	Median progression free survival (PFS) of GSK1363089		4 months (average)	No
Secondary	Duration of Stable Disease of GSK1363089		4 months (average)	No
Secondary	Peak and trough concentrations of GSK1363089 in plasma samples		first 8 weeks of study treatment	No
Secondary	Disease stabilization rate of GSK 1363089		4 months (average)	No
Secondary	Median overall survival of GSK1363089		6 months (average)	No
Secondary	Plasma concentrations of soluble MET, HGF, soluble VEGFR2 and VEGFA		first 8 weeks of study treatment	No

External Links

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