Safety and Efficacy of TKI258 in FGFR1 Amplified and Non-amplified Metastatic HER2 Negative Breast Cancer

December 11, 2020 updated by: Novartis Pharmaceuticals

A Multi-center, Open Label Phase II Trial of TKI258 in FGFR1 Amplified and Non-amplified Metastatic or Advanced HER2 Negative Breast Cancer

The purpose of this trial is to determine the efficacy and safety profile of TKI258 in 3 groups of patients with metastatic HER2 negative breast cancer (BC) stratified by FGFR1 and hormone receptor (HR) status.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

43

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Novartis Investigative Site
    • Quebec
      • Montreal, Quebec, Canada, H2W 1T8
        • Novartis Investigative Site
  • Finland
      • Helsinki, Finland, FIN-00029
        • Novartis Investigative Site
  • France
      • Lyon Cedex, France, 69373
        • Novartis Investigative Site
      • Saint-Herblain Cédex, France, 44805
        • Novartis Investigative Site
      • Toulouse Cedex 3, France, 31052
        • Novartis Investigative Site
      • Villejuif Cedex, France, 94805
        • Novartis Investigative Site
  • Italy
      • Napoli, Italy, 80131
        • Novartis Investigative Site
      • Negrar, Italy, 37024
        • Novartis Investigative Site
    • CN
      • Cuneo, CN, Italy, 12100
        • Novartis Investigative Site
    • CR
      • Cremona, CR, Italy, 26100
        • Novartis Investigative Site
    • PR
      • Parma, PR, Italy, 43100
        • Novartis Investigative Site
    • TO
      • Candiolo, TO, Italy, 10060
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28041
        • Novartis Investigative Site
    • Cataluña
      • Barcelona, Cataluña, Spain, 08035
        • Novartis Investigative Site
      • Lleida, Cataluña, Spain, 25198
        • Novartis Investigative Site
  • Taiwan
      • Taipei, Taiwan, 10048
        • Novartis Investigative Site
  • United Kingdom
      • Glasgow, United Kingdom, G12 0YN
        • Novartis Investigative Site
      • London, United Kingdom, SE1 9RT
        • Novartis Investigative Site
      • London, United Kingdom, SW3 6JJ
        • Novartis Investigative Site
  • United States
    • California
      • Bakersfield, California, United States, 93309
        • Comprehensive Blood and Cancer Center Dept CBCC (3)
      • Beverly Hills, California, United States, 90211
        • Tower Cancer Research
      • Los Angeles, California, United States, 90095
        • UCLA/ University of California Los Angeles Div. of Hematology/Oncology
      • Redondo Beach, California, United States, 90277
        • Cancer Care Associates Medical Group Dept. of CCA
      • Santa Maria, California, United States, 93454
        • Central Coast Medical Oncology Corporation
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Florida Cancer Specialists Dept.of FloridaCancerSpec. (2)
    • Kansas
      • Overland Park, Kansas, United States, 66210
        • Kansas City Cancer Center KCCC (3)
    • Maryland
      • Rockville, Maryland, United States, 20850
        • Associates in Oncology/Hematology, P.C.
    • Nevada
      • Henderson, Nevada, United States, 89052
        • Comprehensive Cancer Centers of Nevada
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7295
        • UNC/ Lineberger Comprehensive Cancer Center Dept. of Linberger Cancer Ctr
    • Oregon
      • Portland, Oregon, United States, 97210
        • Northwest Cancer Specialists Northwest Office (2)
    • Texas
      • Bedford, Texas, United States, 76022
        • Texas Oncology, P.A. Dept. of Texas Oncology
      • Dallas, Texas, United States, 75246
        • Texas Oncology, P.A. Austin
      • Dallas, Texas, United States, 75246
        • Texas Oncology, P.A. Presbyterian Hospital
      • Dallas, Texas, United States, 75246
        • Texas Oncology, P.A. Texas Oncology - Sammons
      • Tyler, Texas, United States, 75702
        • Tyler Cancer Center Dept.ofTylerCancerCtr. (2)
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Fairfax Northern Virginia Hematology Oncology Fairfax NVH
      • Roanoke, Virginia, United States, 24014
        • Blue Ridge Research Center at Roanoke Neurological Center Blue Ridge Cancer Care

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Female presenting with metastatic breast cancer.
  2. Tumor must have been tested by FISH/CISH for FGFR1 amplification.
  3. HER2 and HR status must have been determined.
  4. Patients must have HER2 negative breast cancer.
  5. Patients must have a documented disease progression as define by RECIST at baseline.

  6. Patients with HR+ disease:

    • Must have received at least one prior endocrine therapy in the metastatic setting.
    • Must have received no more than three lines of chemotherapy in the metastatic setting.
  7. Patients with HR- disease must have received at least one and no more than three lines of chemotherapy in metastatic setting.

Exclusion Criteria:

  1. Patients with known brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases.

  2. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

    • History or presence of serious uncontrolled ventricular arrhythmias or presence of atrial fibrillation.
    • Clinically significant resting bradycardia (< 50 beats per minute).
    • LVEF assessed by 2-D echocardiogram (ECHO) or Multiple gated acquisition scanning (MUGA)< 45%.
  3. Any of the following within 6 months prior to study entry: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE).
  4. Uncontrolled hypertension defined by a SBP > 150mm Hg and/or DBP > 100mm Hg, with or without anti-hypertensive medication.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TKI258 - Positive
These are the participants who had a positive T(4;14) status
Drug: TKI258
All participants received a singly daily oral dose of 500 mg dovitinib on a 5 days on/2 days off schedule in 28 cycles.
Other Names:
  • Dovitinib
Experimental: TKI258 - Negative
These are the participants who had a negative T(4;14) status
Drug: TKI258
All participants received a singly daily oral dose of 500 mg dovitinib on a 5 days on/2 days off schedule in 28 cycles.
Other Names:
  • Dovitinib
Experimental: TKI258 Non-interpretable
These are the participants who had a non-interpretable T(4;14) status
Drug: TKI258
All participants received a singly daily oral dose of 500 mg dovitinib on a 5 days on/2 days off schedule in 28 cycles.
Other Names:
  • Dovitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Complete responses (CR) or partial response (PR) defined according to RECIST
Time Frame: Every 8 weeks
Every 8 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Clinical Benefit (CR, PR and SD ≥ 24 weeks after start of study treatment), PFS
Time Frame: Every 8 weeks
Every 8 weeks
Safety and tolerability of TKI258 treatment assessed by frequency and severity of Adverse Events.
Time Frame: Monthly
Monthly
Pharmacokinetic: plasma concentrations and PK parameters (e.g. Cmax, Tmax, AUC0-t)
Time Frame: Study Day 1, 5 , 26, 52, 78
Study Day 1, 5 , 26, 52, 78

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2009

Primary Completion (Actual)

March 1, 2011

Study Completion (Actual)

March 1, 2011

Study Registration Dates

First Submitted

August 11, 2009

First Submitted That Met QC Criteria

August 12, 2009

First Posted (Estimate)

August 14, 2009

Study Record Updates

Last Update Posted (Actual)

December 19, 2020

Last Update Submitted That Met QC Criteria

December 11, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTKI258A2202
  • 2008-006430-10 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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