Clinical trial NCT00958971: Safety and Efficacy of TKI258 in FGFR1 Amplified and Non-amplified Metastatic HER2 Negative Breast Cancer
Official title: A Multi-center, Open Label Phase II Trial of TKI258 in FGFR1 Amplified and Non-amplified Metastatic or Advanced HER2 Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Keywords: Breast cancer
HER2 negative
FGFR1
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-08-14
Enrollment: 43
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Complete responses (CR) or partial response (PR) defined according to RECIST
timeFrame: Every 8 weeks
Secondary outcomes:
measure: Clinical Benefit (CR, PR and SD ≥ 24 weeks after start of study treatment), PFS
timeFrame: Every 8 weeks
measure: Safety and tolerability of TKI258 treatment assessed by frequency and severity of Adverse Events.
timeFrame: Monthly
measure: Pharmacokinetic: plasma concentrations and PK parameters (e.g. Cmax, Tmax, AUC0-t)
timeFrame: Study Day 1, 5 , 26, 52, 78
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center Dept CBCC (3)
state: California
city: Beverly Hills
country: United States
facility: Tower Cancer Research
state: California
city: Los Angeles
country: United States
facility: UCLA/ University of California Los Angeles Div. of Hematology/Oncology
state: California
city: Redondo Beach
country: United States
facility: Cancer Care Associates Medical Group Dept. of CCA
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists Dept.of FloridaCancerSpec. (2)
state: Florida
city: Overland Park
country: United States
facility: Kansas City Cancer Center KCCC (3)
state: Kansas
city: Rockville
country: United States
facility: Associates in Oncology/Hematology, P.C.
state: Maryland
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Chapel Hill
country: United States
facility: UNC/ Lineberger Comprehensive Cancer Center Dept. of Linberger Cancer Ctr
state: North Carolina
city: Portland
country: United States
facility: Northwest Cancer Specialists Northwest Office (2)
state: Oregon
city: Bedford
country: United States
facility: Texas Oncology, P.A. Dept. of Texas Oncology
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A. Austin
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A. Presbyterian Hospital
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A. Texas Oncology - Sammons
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center Dept.ofTylerCancerCtr. (2)
state: Texas
city: Fairfax
country: United States
facility: Fairfax Northern Virginia Hematology Oncology Fairfax NVH
state: Virginia
city: Roanoke
country: United States
facility: Blue Ridge Research Center at Roanoke Neurological Center Blue Ridge Cancer Care
state: Virginia
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Helsinki
country: Finland
facility: Novartis Investigative Site
city: Lyon Cedex
country: France
facility: Novartis Investigative Site
city: Saint-Herblain Cédex
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex 3
country: France
facility: Novartis Investigative Site
city: Villejuif Cedex
country: France
facility: Novartis Investigative Site
city: Cuneo
country: Italy
facility: Novartis Investigative Site
state: CN
city: Cremona
country: Italy
facility: Novartis Investigative Site
state: CR
city: Parma
country: Italy
facility: Novartis Investigative Site
state: PR
city: Candiolo
country: Italy
facility: Novartis Investigative Site
state: TO
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Negrar
country: Italy
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Lleida
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: