Study of GSK1363089 in Metastatic Gastric Cancer

NCT00725712 | Completed Phase 2 Results

• 1 other identifier: MET111643
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 17

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.

Conditions

Neoplasms, Gastrointestinal Tract

Keywords

c-Met; Metastatic Gastric Carcinoma; adenocarcinoma; Gastric cancer; GSK1363089; XL880; MET inhibitor

Outcome Measures

Primary Outcomes (12)

• Number of Participants With Objective Response Rate (ORR), of GSK1363089, Per- Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Version 1.0

  ORR is defined as the percentage of participants achieving best overall response of confirmed complete response (CR) or partial response (PR). Tumor response for participants with measurable lesions was assessed routinely (after 8 weeks of treatment and approximately every 8 weeks thereafter) using RECIST (version 1.0) criteria. The CR for target lesions was defined as disappearance of all target lesions (TLs) and the non-target lesions (NTLs). PR defined as at least 30% decrease in sum of the longest diameter (LD) of TLs, taking as reference baseline sum LD. The safety population included all participants who passed the screening criteria, enrolled in the study, and received at least 1 dose of study drug. Progressive disease will be used as PD.

  At every 8 Weeks upto 31 months

• Number of Participants With Adverse Event (AE) and Serious Adverse Event (SAE)

  An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product whether or not it is considered drug related. This would include any side effect, injury, toxicity, sensitivity reaction, abnormal or worsening of a laboratory value, concurrent illness or sudden death. Pre-existing conditions that worsen during a study will be reported as AEs. SAE is an AE that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered SAEs if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above.

  Up to 31 months

• Change From Baseline in Vital Signs-Systolic and Diastolic Blood Pressure

  Participants systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in mm of mercury (mmHg). These were collected after the participant sat quietly for at least five minutes. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. The data for minimum (min) and maximum (max) post-baseline has been reported. Baseline is defined as the last non-missing record on or before first dose.

  Baseline (pre-dose, Day 1) and before 30-day follow- up (up to 2 years)

• Change From Baseline in Vital Signs-Pulse Rate

  The pulse rate or heart rate (HR) for the participant's, were collected after the participant sat quietly for at least five minutes. Baseline evaluations were performed within 72 hours before the first dose. If performed within 24 hours of the first dose, baseline evaluations may serve as the pre-dose Day 1 visit evaluations. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline was defined as pre-dose, Day 1. The HR was measured in beats per minute (bpm). The min and max values have been reported.

  Baseline (pre-dose, Day 1) and before 30-day follow- up (up to 2 years)

• Change From Baseline in Temperature

  The body temperature for the participants was assessed. These were collected after the participant sat quietly for at least five minutes. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. Baseline is defined as the last non-missing record on or before first dose.

  Baseline (pre-dose, Day 1) and before 30-day follow- up (up to 2 years)

• Change From Baseline in Respiratory Rate (RR)

  The RR for the participant's, were collected after the participant sat quietly for at least five minutes. Baseline evaluations should be performed within 72 hours before the first dose. If performed within 24 hours of the first dose, baseline evaluations may serve as the pre-dose Day 1 visit evaluations. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as pre-dose, Day 1 . The RR was measured in breaths per minute. Min and max post-baseline values are reported.

  Baseline (pre-dose, Day 1) and before 30-day follow- up (up to 2 years)

• Number of Participants With Shift From Baseline in by High/Low Flag for Serum Chemistry- Ungraded

  The data for serum chemistry parameters like albumin, alanine aminotransferase (ALT), alkaline phosphatase (ALP), amylase, aspartate amino transferase (AST), calcium, carbon dioxide, creatinine, gamma glutamyl transferase (GGT), glucose, blood urea nitrogen (BUN), chloride, free thyroxine, free triiodothyronine, lipase, phosphorous, potassium, sodium, total bilirubin, lactate dehydrogenase, total protein. The abnormal values have been reported wherein data for normal to low and normal to high has been reported.

  From Day 1 and before 30-day follow- up (up to 2 years)

• Number of Participants With Shift From Baseline in Serum Chemistry- Graded

  The worst overall common terminology criteria for adverse events version 3.0 (CTCAE) grade (G) shift post baseline for each parameter was mentioned. Only worst case scenarios are presented. CTCAE grading is done as per intensity namely mild moderate severe life-threatening or Death. Analysis was done for Alanine aminotransferases, aspartate aminotransferases, Albumin, alkaline phosphatase, calcium, sodium, potassium, glucose, amylase, amylase, bilirubin, creatinine, phosphate, gamma glutamyl transferases (GGT), and triglycerol lipase. Worst Overall defined as worst post baseline out of normal range flag in the order of (high, low, normal) before 30 day follow up. Data for G3 and G4 is reported.

  From Day 1 to up to 30-day follow-up visit (up to 2 years)

• Number of Participants With Shift From Baseline by High/Low Flag for Hematology Paramaters

  The hematology parameters worst case overall CTCAE grade shift post Baseline for each parameter was mentioned. CTCAE grading for version 3.0 was used and done as per intensity namely mild moderate severe life-threatening or Death. Participants were analyzed for basophils, eosinophils, erythrocytes, hematocrit, and monocytes were analyzed. Only the abnormal values were reported where normal to high and normal to low changes were reported. Worst Overall was defined as highest post baseline CTCAE grade before 30 day follow up.

  From Day 1 and before 30-day follow- up (up to 2 years)

• Number of Participants With Grade Shift for Urinalysis Parameters

  The urinalysis parameters by worst case overall CTCAE grade shift post Baseline for each parameter were mentioned as per the CTCAE grading for version 3.0 and done as per intensity namely mild moderate severe life-threatening or Death. Participants were analyzed for abnormal values for bilirubin, ketones, nitrites, occult blood, pH, protein, specific gravity, and urobilinogen.

  From Day 1 and before 30-day follow- up (up to 2 years)

• Number of Participants With Shift From Baseline by Grade for Hematology Parameters

  The worst overall grading by CTCAE version 3.0, was used to report the shift from baseline for hematology parameters namely hemoglobin, platelets and lymphocytes. The grades were namely G0, G1, G2, G3 and G4. The data for shifts from G2 to G3 and G0 to G4, mainly the shifts to higher grades G3 and G4 have been reported.

  Baseline (pre-dose) and before 30-day follow- up (up to 2 years)

• Number of Participants Who Required Concomitant Medications

  The number of participants who received concomitant medication during the study were reported. The data has been reported for the participants who have received subsequent chemotherapy, subsequent radiation therapy or other therapy.

  Baseline (pre-dose) and before 30-day follow- up (up to 2 years)

Secondary Outcomes (4)

• Median Progression Free Survival (PFS) of GSK1363089

  At every 8 Weeks upto 31 months

• Duration of Stable Disease of GSK1363089

  At every 8 Weeks upto 31 months

• Disease Stabilization Rate of GSK 1363089

  At every 8 Weeks upto 31 months

• Median Duration of Overall Survival (OS)of GSK1363089

  At every 8 Weeks upto 31 months

Study Arms (2)

5-days on/9-days off

EXPERIMENTAL

Dosing for first 5 days in every 14-day period.

Drug: GSK1363089 (formerly XL880)

daily dosing

EXPERIMENTAL

dosed every day

Drug: GSK1363089 (formerly XL880)

Interventions

GSK1363089 (formerly XL880) DRUG

c-MET tyrosine kinase inhibitor

Also known as: foretinib

5-days on/9-days off; daily dosing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (17)

GSK Investigational Site

Birmingham, Alabama, 35294, United States

Location

GSK Investigational Site

Scottsdale, Arizona, 85258, United States

Location

GSK Investigational Site

Los Angeles, California, 90024, United States

Location

GSK Investigational Site

Stanford, California, 94305, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20007, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30309, United States

Location

GSK Investigational Site

Chicago, Illinois, 60637, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02114, United States

Location

GSK Investigational Site

Detroit, Michigan, 48201, United States

Location

GSK Investigational Site

Billings, Montana, 59101, United States

Location

GSK Investigational Site

Albuquerque, New Mexico, 87131, United States

Location

GSK Investigational Site

New York, New York, 10016, United States

Location

GSK Investigational Site

New York, New York, 10021, United States

Location

GSK Investigational Site

Durham, North Carolina, 27710, United States

Location

GSK Investigational Site

Portland, Oregon, 97239, United States

Location

GSK Investigational Site

Austin, Texas, 78705, United States

Location

GSK Investigational Site

Madison, Wisconsin, 53792, United States

Location

Related Publications (3)

• 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.

  PMID: 23516391 BACKGROUND

• 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.

  RESULT

• 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

  RESULT

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Neoplasms; Stomach Neoplasms; Adenocarcinoma

Interventions

GSK 1363089

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2008
• First Posted: July 30, 2008
• Study Start: March 31, 2007
• Primary Completion: November 1, 2009
• Study Completion: November 30, 2009
• Last Updated: August 24, 2017
• Results First Posted: August 24, 2017

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will share

Locations

US (17)