In female patients with FGFR1 amplified and non-amplified metastatic HER2 negative breast cancer. MedDRA version: 9.1 Level: LLT Classification code 10006187 Term: Breast cancer
Conditions
Interventions
Product Name: TKI258
Product Code: TKI258
Pharmaceutical Form: Capsule, hard
Current Sponsor code: TKI258
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Produ
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female patients with histological confirmation of adenocarinoma of the breast, presenting with metastatic disease. 2. The primary tumor, metastatic axillary lymph nodes or biopsy of metastatic tumor must have been tested by FISH/CISH/SISH for FGFR1 amplification before study entry. Tumor material must be available for central testing. 3. HER2 and hormone receptors (ER/PgR) status of breast cancer must have been previously determined. 4. Patients must have HER2 negative breast cancer. 5. Patients must have a documented disease progression as defined by RECIST at baseline. 6. Patients must have at least one measurable lesion as defined by RECIST 7. Patients with HR+ disease must have received: • at least 1 prior endocrine therapy in the metastatic setting • no more than 3 lines of chemotherapy in the metastatic setting 8. Patients with HR- disease must have received at least 1 and no more than 3 lines of chemotherapy in metastatic setting 9. Patient must be = 18 years old. 10. Patient’s WHO performance status equal to 0, 1 or 2. Required baseline laboratory values: 11. Absolute Neutrophil Count (ANC) = 1.5 x 109/L 12. Hemoglobin = 9 g/dl 13. Platelets = 100 x 109/L 14. Serum creatinine = 1.5 x ULN 15. AST/SGOT and ALT/SGPT = 2.5 x Upper Limit of Normal (ULN) or = 5.0 x ULN if liver metastases are present 16. Serum bilirubin = 1.5 x ULN 17. All patients must have signed and dated an informed consent form. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with brain metastases as assessed by radiologic imaging (e.g. CT, MRI). (Please note: The radiological confirmation is required for all patients at the baseline screening visit.) 2. Patients with history of another malignancy within the last 5 years prior to study entry, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix. 3. Patients who have received the last administration of chemotherapy or immunotherapy or hormone therapy = the timeframe defined below after the end of the cycle of the last treatment, prior to starting study drug, or who have not recovered from the side effects of such therapy: patients who have received the last administration of chemotherapy/immunotherapy/hormone therapy in a daily schedule = 7 days prior to starting study drug; patients who have received the last administration of chemotherapy/immunotherapy/hormone therapy in a weekly schedule = 2 weeks prior to starting study drug; patients who have received the last administration of chemotherapy/immunotherapy/hormone therapy in a 2-weekly schedule = 3 weeks prior to starting study drug; patients who have received the last administration of chemotherapy/immunotherapy/hormone therapy in a 3-weekly schedule = 4 weeks prior to starting study drug; patients who have received the last administration of chemotherapy/ immunotherapy/hormone therapy in a 4-weekly schedule = 5 weeks prior to starting study drug. Patients who have received the last administration of nitrosourea, mitomycin-C = 6 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy. 4. Patients who received a continuous dosing small molecule therapeutic = 7 days prior to starting study drug or who have not recovered from the side effects of such therapy 5. Patients who received the last administration of biologic therapy = 6 weeks prior to starting study drug or who have not recovered from the side effects of such therapy 6. Patients who have received any other investigational agents = 4 weeks prior to starting study drug or who have not recovered from the side effects of such therapy 7. Patients who have received wide field radiotherapy = 4 weeks or limited field radiation for palliation = 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy. 8. Patients who have undergone major surgery = 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy. Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study : 9. 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 ( 150 mm Hg and/or DBP > 100 mm Hg, with or without anti-hypertensive medication. 12. Previous pericarditis; clinically significant pleural effusion in the previous 12 months or current ascites requiring two or more interventio
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To determine the Overall Response Rate (ORR) in 4 groups of patients with (FGFR1+, HR+),(FGFR1+, HR-),(FGFR1-, HR+) or (FGFR1-, HR-) metastatic breast cancer treated with TKI258.;Primary end point(s): • Overall Response (Complete responses (CR) or partial response (PR)) Rate. CR and PR will be defined according to RECIST.;Secondary Objective: • To determine Disease Control Rate (DCR), defined according to RECIST, (CR, PR and Stable Disease (SD) = 24 weeks after start of TKI258 treatment) in the 4 groups of patients • Progression Free Survival (PFS), defined according to RECIST, in the 4 groups of patients. • To characterize the safety and tolerability of TKI258 treatment. • To determine the trough plasma concentration of TKI258 following repeated-dose. | — |
Countries
Finland, France, Italy, Spain, United Kingdom
Outcome results
None listed