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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors; Excluding Breast Cancer
• Intervention / Treatment: Drug: TKI258

• Study Type: Interventional
• Enrollment (Actual): 166
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope National Medical Center SC-2
    • Los Angeles, California, United States, 90095
      • University of California at Los Angeles UCLA LeConte Location
    • San Francisco, California, United States, 94101
      • University of California San Francisco UCSF (SC)
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists Sarasota Office
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center Rush 3
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine SC
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center Montefiore Medical Center (SC)
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center OUHSC - SC
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232-1305
      • University of Pittsburgh Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute Sarah Cannon Research (SC)
  • Texas
    • Dallas, Texas, United States, 78246
      • Sammons Cancer Center - Texas Oncology SC-2
    • San Antonio, Texas, United States, 78229
      • Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(5)
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah / Huntsman Cancer Institute Huntsman
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Univ Wisc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 500 mg FMI capsule + 250 mg FMI tablet; BE phase sequence 1= 3 weeks on FMI capsule then 1 week on FMI tablet	Drug: TKI258; Other Names: dovitinib
Experimental: 500 mg TKI258 FMI capsule +250 mg FMI tablet; BE phase sequence 2= 3 weeks on FMI tablet then 1 week on FMI capsule	Drug: TKI258; Other Names: dovitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartitis Pharmaceuticals, Novartitis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CTKI258A2128 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: August 11, 2011
• First Submitted That Met QC Criteria: August 19, 2011
• First Posted (Estimate): August 22, 2011

Study Record Updates

• Last Update Posted (Actual): December 21, 2020
• Last Update Submitted That Met QC Criteria: December 17, 2020
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: cancer; bioequivalence; phase I; tumors; crossover
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CTKI258A2128