Clinical trial NCT00725712: Study of GSK1363089 in Metastatic Gastric Cancer
Official title: A Phase 2 Study of GSK1363089 (XL880) Administered Orally to Subjects With Metastatic Gastric Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasms, Gastrointestinal Tract
Keywords: c-Met
Metastatic Gastric Carcinoma
adenocarcinoma
Gastric cancer
GSK1363089
XL880
MET inhibitor
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-07-30
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Objective Response Rate (ORR), of GSK1363089, Per- Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Version 1.0
timeFrame: At every 8 Weeks upto 31 months
measure: Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE)
timeFrame: Up to 31 months
measure: Change From Baseline in Vital Signs-Systolic and Diastolic Blood Pressure
timeFrame: Baseline (pre-dose, Day 1) and before 30-day follow- up (up to 2 years)
measure: Change From Baseline in Vital Signs-Pulse Rate
timeFrame: Baseline (pre-dose, Day 1) and before 30-day follow- up (up to 2 years)
measure: Change From Baseline in Temperature
timeFrame: Baseline (pre-dose, Day 1) and before 30-day follow- up (up to 2 years)
measure: Change From Baseline in Respiratory Rate (RR)
timeFrame: Baseline (pre-dose, Day 1) and before 30-day follow- up (up to 2 years)
measure: Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded
timeFrame: From Day 1 and before 30-day follow- up (up to 2 years)
measure: Number of Participants With Shift From Baseline in Serum Chemistry- Graded
timeFrame: From Day 1 to up to 30-day follow-up visit (up to 2 years)
measure: Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters
timeFrame: From Day 1 and before 30-day follow- up (up to 2 years)
measure: Number of Participants With Grade Shift for Urinalysis Parameters
timeFrame: From Day 1 and before 30-day follow- up (up to 2 years)
measure: Number of Participants With Shift From Baseline by Grade for Hematology Parameters
timeFrame: Baseline (pre-dose) and before 30-day follow- up (up to 2 years)
measure: Number of Participants Who Required Concomitant Medications
timeFrame: Baseline (pre-dose) and before 30-day follow- up (up to 2 years)
Secondary outcomes:
measure: Median Progression Free Survival (PFS) of GSK1363089
timeFrame: At every 8 Weeks upto 31 months
measure: Duration of Stable Disease of GSK1363089
timeFrame: At every 8 Weeks upto 31 months
measure: Disease Stabilization Rate of GSK 1363089
timeFrame: At every 8 Weeks upto 31 months
measure: Median Duration of Overall Survival (OS)of GSK1363089
timeFrame: At every 8 Weeks upto 31 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Scottsdale
country: United States
facility: GSK Investigational Site
state: Arizona
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Stanford
country: United States
facility: GSK Investigational Site
state: California
city: Washington, D.C.
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: GSK Investigational Site
state: Michigan
city: Billings
country: United States
facility: GSK Investigational Site
state: Montana
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Durham
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Portland
country: United States
facility: GSK Investigational Site
state: Oregon
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Madison
country: United States
facility: GSK Investigational Site
state: Wisconsin
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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 II study J Clin Oncol 2009, 27 (15S), 4502.
citation: 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 multicenter phase 2 study. J Clin Oncol, 2008, 26 (15S), Abstr. 4572