An exploratory clinical study to evaluate the safety and efficacy of the new medicine TKI258 together with fulvestrant (a currently used medicinal product in the treatment of advanced breast cancer) compared to fulvestrant alone in postmenopausal women with specific kind of advanced breast cancer which has progressed after prior hormonal therapy
- Conditions
- Breast cancer, HER2 negative and HR positive, with evidence of disease progression after prior endocrine therapyMedDRA version: 14.1Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-001230-42-IT
- Lead Sponsor
- OVARTIS FARMA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 150
1.Written informed consent obtained prior to any study procedures, including screening assessments. 2.Postmenopausal (= 18 years) women with HER2-, HR+ (ER+ and/or PgR+), locally advanced or metastatic breast cancer not amenable to curative treatment by surgery or radiotherapy. Postmenopausal status is defined either by: a) Age = 55 years and one year or more of amenorrhea, or b) Age < 55 years and one year or more of amenorrhea in the absence of ovarian suppression, with an estradiol assay < 20 pg/mL, or c) Surgical menopause with bilateral oophorectomy. Note that it is not possible to assign menopause status to women who are receiving an LHRH agonist or antagonist. 3.Breast cancer that has progressed on or after prior endocrine therapy, with radiological evidence of recurrence or progression as follows: a) While on, or within 12 months of end of adjuvant treatment with any endocrine therapy (e.g., tamoxifen, exemestane, anastrozole, letrozole, etc.); b) While on, or within 1 month of end of any endocrine therapy treatment for LA/mBC. 4. Have measurable disease as per RECIST v1.1 (Appendix 1) or nonmeasurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease. Patients with only non-measurable lesions and no lytic or a mix of lytic and sclerotic bone metastasis (e.g. pleural effusion, ascites) are not eligible. Note: a) measurable lesions include lytic or mixed (lytic + blastic) bone lesions with an identifiable soft tissue component that meets the measurability criteria per RECIST v1.1, and; b) lesions in previously irradiated areas should not be considered measurable, unless they have clearly progressed since the radiotherapy. 5.Eastern Cooperative Oncology Group (ECOG) performance status that is not greater than 2 (i.e., either 0 or 1 or 2). 6.Have the following laboratory values: a) Absolute neutrophil count (ANC) = 1.5 x 109/L; b) Platelets = 100 x 109/L; c) Hemoglobin (Hgb) > 9 g/dL; d) Serum total bilirubin = 1.5 x ULN; e) ALT and AST = 3.0 x ULN (with or without liver metastases); f) Serum creatinine = 1.5 x ULN or Creatinine clearance by 24 hr urine is = 30 mL/min OR: Serum creatinine >1.5 - 3 x ULN with calculated creatinine clearance (CrCl) is = 30 mL/min using the Cockroft-Gault equation, per the formula provided here: CrCl = ([140-age (years)] x weight (kg) / [72 x serum Cr (mg/dL)]) x .85. 7. Have completely recovered from major effects of prior radiotherapy and from any drug-related adverse events (AEs) associated with previous treatments, excluding alopecia and grade 1 peripheral neuropathy according to the National Cancer Institute CTCAE, v. 4.03. 8.Provide archival (paraffin embedded tissue or a minimum of 20 unstained slides) or fresh tumor tissues from which the FGF pathway status can be determined by an Novartis designated laboratory.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Evidence of central nervous system or leptomeningeal metastases.2. HER2 over expression as depicted IHC 3+ or FISH testing.3. Previously treated with fulvestrant as a single agent or in combination with other therapies or FGFR inhibitors.4. Have any contraindication for being treated with fulvestrant 500 mg as described in the local approved prescribing information.5.Received more than one line of any prior hormonal therapy for LA/mBC.6.Any adjuvant/neo adjuvant therapy is allowed. 7.Received any chemotherapy for LA/mBC. 8.Concurrent use of any other approved or investigational anticancer agents, including hormonal agents.9.Having participated in a prior investigational study within 30 days prior to enrollment or = 5 half-lives of the investigational product, whichever is longer.10.Received the last administration of anti-cancer targeted small molecule therapy (e.g. sunitinib, sorafenib, pazopanib, axitinib, everolimus, temsirolimus, radaforolimus) = 2 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy.11.Received the last administration of an anti-cancer monoclonal antibody, immunotherapy, hormonal therapy, or chemotherapy (except nitrosoureas and mitomycin-C) = 4 weeks prior to starting study drug or who have not recovered from the side effects of such therapy.12.Received the last administration of nitrosourea or mitomycin-C = 6 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy.13. Received radiotherapy = 4 weeks prior to starting the study drug or who have not recovered from radiotherapy-related toxicities (palliative radiotherapy for bone lesions = 2 weeks prior to starting study drug is allowed).14.Undergone major surgery = 4 weeks prior to starting study drug or who have not recovered from side effects of such surgery.15.With a history of pulmonary embolism (PE), or untreated deep venous thrombosis (DVT) = 6 months prior to starting study drug Impaired cardiac function or clinically significant cardiac diseases, including any of the following: a) History or presence of serious uncontrolled ventricular arrhythmias; b) Clinically significant resting bradycardia (< 50 beats /minute); c) LVEF assessed by 2-D echocardiogram (ECHO) < 50% or lower limit of normal (whichever is higher) or multiple gated acquisition scan (MUGA) < 45% or lower limit of normal (whichever is higher); d) Any of the following within 6 months prior to starting study drug: myocardial infarction, severe/unstable angina, coronary artery bypass graft, congestive heart failure, cerebrovascular accident, transient ischemic attack; e) Uncontrolled hypertension defined by a SBP = 160 mm Hg and/or DBP = 100 mm Hg, with or without anti-hypertensive medication(s). Initiation or adjustment of antihypertensive medication(s) is allowed prior to study entry.16.Currently receiving anti-platelet therapy of prasugrel or clopidogrel, or full dose anticoagulation treatment with therapeutic doses of warfarin. However, treatment with low doses of warfarin (e.g., = 2 mg/day) or locally accepted low doses of acetylsalicylic acid (up to 100 mg daily) to prevent cardiovascular events or strokes is allowed.17.Concurrent malignancy or malignancy within 3 years prior to study enrollment, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or in-situ carcinoma of the uterine cervix. For further details please see the
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method