A Dose Escalation Study of the Safety and Pharmacokinetics of GSK1363089 (Formerly XL880) Administered Orally Daily to Subjects With Solid Tumors

Study Overview
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Brief Summary
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This clinical study is being conducted at two sites to determine the optimum dose, safety, and tolerability of oral daily GSK1363089 treatment in adults with solid tumors. This study is no longer recruiting subjects.

Official Title
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A Phase 1 Dose Escalation Study of the Safety and Pharmacokinetics of GSK1363089 (Formerly XL880) Administered Orally Daily to Subjects With Solid Tumors

Conditions
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Solid Tumours

Intervention / Treatment
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* Drug: GSK1363089 (formerly XL880)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed solid tumor which is metastatic or unresectable with no known effective treatment measures, ECOG performance status of </= 2. Adequate bone marrow reserve, hepatic, renal, and cardiovascular function, Negative pregnancy test. Exclusion Criteria: Anticancer therapy within 30 days of the start of treatment, Received radiation to =25% of bone marrow within 30 days of treatment. Known brain metastasis, Uncontrolled intercurrent illness, HIV positive, Pregnant or breastfeeding women.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Cohort 1 will include 60 milligram (mg) of GSK1363089. Dose escalation will be 100% if there is no drug-related AEs of Grade 2 or higher in previous cohort. Dose escalation will be 50% in case there is Grade 2 drug-related AEs in any previous cohort. | Drug: GSK1363089 (formerly XL880)<br>* GSK1363089 will be available as solid capsules with dose unit of 20, 100 and 200 mg. Subjects will administer GSK1363089 capsules orally<br>|
| Experimental: Cohort 2<br>Cohort 2 will include 120 mg of GSK1363089. Dose escalation will be 100% if there is no drug-related AEs of Grade 2 or higher in previous cohort. Dose escalation will be 50% in case there is Grade 2 drug-related AEs in any previous cohort. | Drug: GSK1363089 (formerly XL880)<br>* GSK1363089 will be available as solid capsules with dose unit of 20, 100 and 200 mg. Subjects will administer GSK1363089 capsules orally<br>|
| Experimental: Cohort 3<br>Cohort 3 will include 240 mg of GSK1363089. Dose escalation will be 100% if there is no drug-related AEs of Grade 2 or higher in previous cohort. Dose escalation will be 50% in case there is Grade 2 drug-related AEs in any previous cohort. | Drug: GSK1363089 (formerly XL880)<br>* GSK1363089 will be available as solid capsules with dose unit of 20, 100 and 200 mg. Subjects will administer GSK1363089 capsules orally<br>|
| Experimental: Cohort 4<br>Cohort 4 will include 480 mg of GSK1363089. Dose escalation will be 100% if there is no drug-related AEs of Grade 2 or higher in previous cohort. Dose escalation will be 50% in case there is Grade 2 drug-related AEs in any previous cohort. | Drug: GSK1363089 (formerly XL880)<br>* GSK1363089 will be available as solid capsules with dose unit of 20, 100 and 200 mg. Subjects will administer GSK1363089 capsules orally<br>|
| Experimental: Cohort 5<br>Cohort 5 will include 960 mg of GSK1363089. Dose escalation will be 100% if there is no drug-related AEs of Grade 2 or higher in previous cohort. Dose escalation will be 50% in case there is Grade 2 drug-related AEs in any previous cohort. | Drug: GSK1363089 (formerly XL880)<br>* GSK1363089 will be available as solid capsules with dose unit of 20, 100 and 200 mg. Subjects will administer GSK1363089 capsules orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the maximum tolerated dose (MTD) and to evaluate the safety and tolerability of daily oral administration of GSK1363089 in subjects with solid tumors |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma pharmacokinetics (PK) of daily GSK1363089 in subjects with solid tumors, pharmacodynamic effects of daily GSK1363089, Long-term safety and tolerability of daily GSK1363089, Tumor response after daily administration of GSK1363089 |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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XL880, MET inhibitor, GSK1363089, Solid Tumors, c-Met