Bioequivalence of 2 Formulations of TKI258 in Patients With Advanced Solid Tumors

Study Overview
=================
Brief Summary
-----------------
This is a multi-center, open-label, two way crossover study designed to test the bioequivalence of 2 different oral forms of TKI258, FMI capsule and FMI tablet in patients with advanced solid tumors, excluding breast cancer. The aim of this test is to demonstrate that those 2 formulations are considered to be the same for all intents and purposes by making sure they are acting on the body with the same strength and are absorbed in similar amounts by the body. During the bioequivalence phase, patients will take orally at a daily dose of 500 mg one formulation of TKI258 during the first 3 weeks of treatment on a 5 days on/2days off dosing schedule, after which time, patients will switch to the alternate formulation for one additional week. After the bioequivalence phase, all patients may continue to take orally at a daily dose of 500 mg only TKI258 FMI capsule formulation until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death or discontinuation from the study treatment for any other reason.

Official Title
-----------------
A Phase I, Open-label, Multi-center, Randomized, Crossover Study to Assess the Bioequivalence of 2 Formulations of TKI258, FMI Capsule and FMI Tablet, in Patients With Advanced Solid Tumors

Conditions
-----------------
Advanced Solid Tumors, Excluding Breast Cancer

Intervention / Treatment
-----------------
* Drug: TKI258


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with a histopathologically or cytopathologically confirmed diagnosis of an advanced solid tumor, excluding breast cancer, who have progressed despite standard therapy, or for which no standard therapy exists ECOG performance status (PS) 0, 1 or 2 Patients must meet protocol-specified laboratory values Exclusion Criteria: Patients with brain metastases Patients who have concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study Patients who have not recovered from previous anti-cancer therapies Patients who are expected to receive any prohibited medications during the bioequivalence phase of the study Female patients who are pregnant, breast feeding Fertile male or women of child-bearing potential not willing to use two highly effective methods of contraception Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 500 mg FMI capsule + 250 mg FMI tablet<br>BE phase sequence 1= 3 weeks on FMI capsule then 1 week on FMI tablet | Drug: TKI258<br> <br> * Other names: dovitinib;|
| Experimental: 500 mg TKI258 FMI capsule +250 mg FMI tablet<br>BE phase sequence 2= 3 weeks on FMI tablet then 1 week on FMI capsule | Drug: TKI258<br> <br> * Other names: dovitinib;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of Pharmacokinetics of TKI258, FMI capsule (supplied in 100 mg strength) and FMI tablet (supplied in 250 mg strength), in patients with advanced solid tumors, excluding breast cancer based on PK parameters AUClast and Cmax |  | 9 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Adverse Events in patients treated with TKI258 on a 5 days on/2 days off dosing schedule in patients with advanced solid tumors, excluding breast cancer |  | up to 30 days after the last dose of study drug | 
| Preliminary evidence of anti-tumor activity based on RECIST criteria of TKI258 in patients with advanced solid tumors, excluding breast cancer |  | Every 8 weeks until progression of disease | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cancer, tumors, phase I, crossover, bioequivalence