Study of GSK1363089 in Metastatic Gastric Cancer
Condition: Neoplasms, Gastrointestinal Tract
MeSH terms: Stomach Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms
Intervention: GSK1363089 (formerly XL880)
Intervention description: c-MET tyrosine kinase inhibitor
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: c-Met; Metastatic Gastric Carcinoma; adenocarcinoma; Gastric cancer; GSK1363089; XL880; MET inhibitor

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.