Absorption, Distribution, Metabolism and Excretion (ADME) Study of TKI258 in Patients With Advanced Solid Malignancies

Study Overview
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Brief Summary
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This is a phase l study to examine Absorption, Distribution, Metabolism and Excretion of TKI258. There are 2 cohorts. Cohort 1 (4 patients) will receive single radio-labeled 500mg dose of TKI258 followed after 15 days by daily dosing of 400mg TKI258. Cohort 2 (9 patients) will receive 400mg TKI258.

Official Title
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An Open-Label, Non-Randomized, Single-Center, Phase I Study to Determine the Absorption, Distribution, Metabolism and Excretion (ADME) of TKI258 After a Single Oral Administration of TKI258 500mg and to Assess the Preliminary Safety of TK258 400mg Once Daily in Patients With Advanced Solid Malignancies

Conditions
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Advanced Solid Malignancies

Intervention / Treatment
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* Drug: TKI258


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Aged ≥ 18 years Patients with histologically confirmed solid tumor or lymphoma who are resistant/refractory to approved therapies or for whom no appropriate therapies are available. WHO performance status ≤ 2 All previous treatment (including surgery and radiotherapy) must have been completed at least four weeks prior to study entry and any acute toxicities must have been resolved Written informed consent to participate in the study Exclusion criteria: Primary Brain Tumors or symptomatic leptomeningeal metastases Clinically significant cardiac impairment or unstable ischemic heart disease including a myocardial infarction within six months of study start Fertile males not willing to use contraception or whose female partners are not using adequate contraceptive protection Pregnant or lactating women (all women of childbearing potential must have a negative pregnancy test (> 5 mIU/ml) before inclusion in the study; post-menopausal women must be amenorrheic for at least 12 months). Female patients must use adequate contraceptive protection Centrally located or squamous cell carcinoma of the lung Proteinuria > 1+ on dipstick testing History of gastrointestinal malabsorption Surgery involving intestinal anastomosis within four weeks of study start. Other protocol-defined inclusion/exclusion criteria may apply.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TKI258<br> | Drug: TKI258<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort1: Find out about the routes and rates of excretion of TKI258 and its metabolites |  | Day 15 | 
| Cohort 2: Safety and Tolerability of TKI258 |  | Time to patient withdrawal due to disease progression or tolerability issues | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1: Safety and tolerability of TKI258 |  | Time to patient withdrawal due to disease progression or tolerability issues | 
| Cohort 1: Preliminary anti-tumor activity of TKI258 |  | Time to tumor progression | 
| Preliminary Anti-tumor activity of TKI258 |  | Time to tumor progression | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADME, TKI258, RTKs inhibitor, PDGRF inhibitor, VEGFER inhibitor