Clinical trial NCT01421004: Bioequivalence of 2 Formulations of TKI258 in Patients With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Excluding Breast Cancer
Keywords: cancer
tumors
phase I
crossover
bioequivalence
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-08-22
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. 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
2. ECOG performance status (PS) 0, 1 or 2
3. Patients must meet protocol-specified laboratory values

Exclusion Criteria:

1. Patients with brain metastases
2. Patients who have concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study
3. Patients who have not recovered from previous anti-cancer therapies
4. Patients who are expected to receive any prohibited medications during the bioequivalence phase of the study
5. Female patients who are pregnant, breast feeding
6. 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

Primary outcomes:
measure: 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
timeFrame: 9 days
Secondary outcomes:
measure: 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
timeFrame: up to 30 days after the last dose of study drug
measure: Preliminary evidence of anti-tumor activity based on RECIST criteria of TKI258 in patients with advanced solid tumors, excluding breast cancer
timeFrame: Every 8 weeks until progression of disease
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center SC-2
state: California
city: Los Angeles
country: United States
facility: University of California at Los Angeles UCLA LeConte Location
state: California
city: San Francisco
country: United States
facility: University of California San Francisco UCSF (SC)
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists Sarasota Office
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center Rush 3
state: Illinois
city: Saint Louis
country: United States
facility: Washington University School of Medicine SC
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center Montefiore Medical Center (SC)
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center OUHSC - SC
state: Oklahoma
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute Sarah Cannon Research (SC)
state: Tennessee
city: Dallas
country: United States
facility: Sammons Cancer Center - Texas Oncology SC-2
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(5)
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah / Huntsman Cancer Institute Huntsman
state: Utah
city: Madison
country: United States
facility: University of Wisconsin Univ Wisc
state: Wisconsin
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
affiliation: Novartitis Pharmaceuticals
name: Novartitis Pharmaceuticals
role: STUDY_DIRECTOR
References: