Clinical trial NCT00669097: Absorption, Distribution, Metabolism and Excretion (ADME) Study of TKI258 in Patients With Advanced Solid Malignancies
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Malignancies
Keywords: ADME
TKI258
RTKs inhibitor
PDGRF inhibitor
VEGFER inhibitor
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-04-29
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion criteria:

1. Aged ≥ 18 years
2. Patients with histologically confirmed solid tumor or lymphoma who are resistant/refractory to approved therapies or for whom no appropriate therapies are available.
3. WHO performance status ≤ 2
4. 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
5. Written informed consent to participate in the study

Exclusion criteria:

1. Primary Brain Tumors or symptomatic leptomeningeal metastases
2. Clinically significant cardiac impairment or unstable ischemic heart disease including a myocardial infarction within six months of study start
3. 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
4. Centrally located or squamous cell carcinoma of the lung
5. Proteinuria \> 1+ on dipstick testing
6. History of gastrointestinal malabsorption Surgery involving intestinal anastomosis within four weeks of study start.

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Cohort1: Find out about the routes and rates of excretion of TKI258 and its metabolites
timeFrame: Day 15
measure: Cohort 2: Safety and Tolerability of TKI258
timeFrame: Time to patient withdrawal due to disease progression or tolerability issues
Secondary outcomes:
measure: Cohort 1: Safety and tolerability of TKI258
timeFrame: Time to patient withdrawal due to disease progression or tolerability issues
measure: Cohort 1: Preliminary anti-tumor activity of TKI258
timeFrame: Time to tumor progression
measure: Preliminary Anti-tumor activity of TKI258
timeFrame: Time to tumor progression
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmeceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Dubbelman AC, Upthagrove A, Beijnen JH, Marchetti S, Tan E, Krone K, Anand S, Schellens JH. Disposition and metabolism of 14C-dovitinib (TKI258), an inhibitor of FGFR and VEGFR, after oral administration in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2012 Nov;70(5):653-63. doi: 10.1007/s00280-012-1947-2. Epub 2012 Aug 22.