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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00669097

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Malignancies	Drug: TKI258	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2008

Actual Primary Completion Date :

Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TKI258	Drug: TKI258

Arm

Intervention/Treatment

Experimental: TKI258

Drug: TKI258

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.