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

NCT00958971 | Completed Phase 2 FDA Drug

• 2 other identifiers: CTKI258A22022008-006430-10
• Study Type: interventional
• Target: 43
• Locations: 8 countries
• Sites: 38

Brief Summary

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.

Conditions

Metastatic Breast Cancer

Keywords

Breast cancer; HER2 negative; FGFR1

Outcome Measures

Primary Outcomes (1)

• Complete responses (CR) or partial response (PR) defined according to RECIST

  Every 8 weeks

Secondary Outcomes (3)

• Clinical Benefit (CR, PR and SD ≥ 24 weeks after start of study treatment), PFS

  Every 8 weeks

• Safety and tolerability of TKI258 treatment assessed by frequency and severity of Adverse Events.

  Monthly

• Pharmacokinetic: plasma concentrations and PK parameters (e.g. Cmax, Tmax, AUC0-t)

  Study Day 1, 5 , 26, 52, 78

Study Arms (3)

TKI258 - Positive

EXPERIMENTAL

These are the participants who had a positive T(4;14) status

Drug: TKI258

TKI258 - Negative

EXPERIMENTAL

These are the participants who had a negative T(4;14) status

Drug: TKI258

TKI258 Non-interpretable

EXPERIMENTAL

These are the participants who had a non-interpretable T(4;14) status

Drug: TKI258

Interventions

TKI258 DRUG

All participants received a singly daily oral dose of 500 mg dovitinib on a 5 days on/2 days off schedule in 28 cycles.

Also known as: Dovitinib

TKI258 - Negative; TKI258 - Positive; TKI258 Non-interpretable

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female presenting with metastatic breast cancer.
• Tumor must have been tested by FISH/CISH for FGFR1 amplification.
• HER2 and HR status must have been determined.
• Patients must have HER2 negative breast cancer.
• Patients must have a documented disease progression as define by RECIST at baseline.
• 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.
• Patients with HR- disease must have received at least one and no more than three lines of chemotherapy in metastatic setting.

You may not qualify if:

• 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.
• 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%.
• 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).
• Uncontrolled hypertension defined by a SBP \> 150mm Hg and/or DBP \> 100mm Hg, with or without anti-hypertensive medication.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (38)

Comprehensive Blood and Cancer Center Dept CBCC (3)

Bakersfield, California, 93309, United States

Location

Tower Cancer Research

Beverly Hills, California, 90211, United States

Location

UCLA/ University of California Los Angeles Div. of Hematology/Oncology

Los Angeles, California, 90095, United States

Location

Cancer Care Associates Medical Group Dept. of CCA

Redondo Beach, California, 90277, United States

Location

Central Coast Medical Oncology Corporation

Santa Maria, California, 93454, United States

Location

Florida Cancer Specialists Dept.of FloridaCancerSpec. (2)

Fort Myers, Florida, 33901, United States

Location

Kansas City Cancer Center KCCC (3)

Overland Park, Kansas, 66210, United States

Location

Associates in Oncology/Hematology, P.C.

Rockville, Maryland, 20850, United States

Location

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, 89052, United States

Location

UNC/ Lineberger Comprehensive Cancer Center Dept. of Linberger Cancer Ctr

Chapel Hill, North Carolina, 27599-7295, United States

Location

Northwest Cancer Specialists Northwest Office (2)

Portland, Oregon, 97210, United States

Location

Texas Oncology, P.A. Dept. of Texas Oncology

Bedford, Texas, 76022, United States

Location

Texas Oncology, P.A. Austin

Dallas, Texas, 75246, United States

Location

Texas Oncology, P.A. Presbyterian Hospital

Dallas, Texas, 75246, United States

Location

Texas Oncology, P.A. Texas Oncology - Sammons

Dallas, Texas, 75246, United States

Location

Tyler Cancer Center Dept.ofTylerCancerCtr. (2)

Tyler, Texas, 75702, United States

Location

Fairfax Northern Virginia Hematology Oncology Fairfax NVH

Fairfax, Virginia, 22031, United States

Location

Blue Ridge Research Center at Roanoke Neurological Center Blue Ridge Cancer Care

Roanoke, Virginia, 24014, United States

Location

Novartis Investigative Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H2W 1T8, Canada

Location

Novartis Investigative Site

Helsinki, FIN-00029, Finland

Location

Novartis Investigative Site

Lyon, 69373, France

Location

Novartis Investigative Site

Saint-Herblain Cédex, 44805, France

Location

Novartis Investigative Site

Toulouse, 31052, France

Location

Novartis Investigative Site

Villejuif, 94805, France

Location

Novartis Investigative Site

Cuneo, CN, 12100, Italy

Location

Novartis Investigative Site

Cremona, CR, 26100, Italy

Location

Novartis Investigative Site

Parma, PR, 43100, Italy

Location

Novartis Investigative Site

Candiolo, TO, 10060, Italy

Location

Novartis Investigative Site

Napoli, 80131, Italy

Location

Novartis Investigative Site

Negrar, 37024, Italy

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Lleida, Catalonia, 25198, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Taipei, 10048, Taiwan

Location

Novartis Investigative Site

Glasgow, G12 0YN, United Kingdom

Location

Novartis Investigative Site

London, SE1 9RT, United Kingdom

Location

Novartis Investigative Site

London, SW3 6JJ, United Kingdom

Location

Related Links

• Results for CTKI258A2202 from the Novartis Clinical Trials website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2009
• First Posted: August 14, 2009
• Study Start: July 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: December 19, 2020

Record last verified: 2020-09

Locations

FI (1); TW (1); FR (4); CA (2); IT (6); GB (3); US (18); ES (3)