Advanced Estrogen Receptor-Positive Breast Cancer. MedDRA version: 9.1 Level: LLT Classification code 10006190 Term: Breast cancer invasive NOS
Conditions
Sponsors
Bristol Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Histologically-documented invasive breast cancer, positive for ER and/or PgR in = 10% of tumor cells (institutional determination), with tumor tissue from prior surgery available for analysis. 2) Prior therapy a) Required: a non-steroidal aromatase inhibitor (eg NSAI, letrozole or anastrozole), with exposure of = 12 months in adjuvant setting or = 4 months in advanced setting b) Permitted: tamoxifen, fulvestrant, adjuvant chemotherapy with or without trastuzumab and/or lapatinib, bisphosphonates 3) Recurrent or progressive advanced breast cancer (locally-advanced or metastatic), with = 1 measurable and/or non-measurable (evaluable) tumor, either: a) during or = 12 months after completion of adjuvant NSAI treatment, OR b) during NSAI treatment in advanced setting 4) Documented extent of disease evaluation = 28 days prior to study entry a) CNS metastasis is permitted if asymptomatic without steroid requirement = 8 weeks has elapsed since treatment and is documented to be non-progressing at study entry b) Visceral metastasis (eg, lung, liver) is permitted if asymptomatic, has no effect on Performance Status, and is not associated with abnormal laboratory values 5) Women who are not of childbearing potential (ie, are postmenopausal or surgically sterile) and men, ages = 18. Women are considered surgically sterile only if they have undergone hysterectomy, bilateral tubal ligation, or bilateral oophorectomy. Post menopause is defined as: • Amenorrhea = 12 consecutive months without another cause or • For women with irregular menstrual periods on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL. Women with ovarian suppression due to use of goserelin (Zoladex®) or other LH-RH agonist MUST have a negative pregnancy test prior to investigational drug start. 6) Recovery to Grade 0 - 1 from acute toxicities of prior therapy, except alopecia 7) Performance Status 0 or 1 (see Protocol Appendix 3) 8) Able to take oral medications (dasatinib tablets must be swallowed intact) reliably 9) Signed Written Informed Consent according to Local Regulations 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) Target Disease or Therapy Exclusions a) Pleural or pericardial effusion or ascites (of any etiology; Grade = 1) within 6 months prior to study entry. Trace or ‘minimal’ effusion is acceptable. b) Any chemotherapy, immunotherapy or antibody therapy (eg, bevacizumab) for advanced breast cancer c) Any antitumor therapy, including radiotherapy or hormonal therapy, within 15 days prior to study entry d) Prior exposure to exemestane, to any Src-family kinase inhibitor including dasatinib, to agents intended to control osteolytic metastatic disease other than bisphosphonates, or to any investigational agent for breast cancer 2) Medical History or Concurrent Disease a) Concurrent or previous malignant disease requiring chemotherapy or radiation treatment within the prior 3 years, b) Significant bleeding disorder, including: diagnosed congenital bleeding disorders (eg, von Willebrand’s disease); diagnosed acquired bleeding disorder within 1 year (eg, acquired anti-factor VIII antibodies), or ongoing or recent (= 3 months) clinically-significant gastrointestinal bleeding, c) Serious concomitant systemic disorder, including bacterial, fungal or viral infection requiring intravenous therapy, which in the opinion of Investigator is incompatible with Study, d) Serious cardiac condition, including congestive heart failure or myocardial infarction within 6 months, uncontrolled angina, or Class III or IV heart disease as defined by the New York Heart Association, baseline EF = 40%, diagnosed congenital long QT syndrome, clinically-significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes), QTc interval > 450 msec at baseline (Fridericia correction) 3) Physical and Laboratory Test Findings a) Hematologic abnormality Grade = 2 b) Hypocalcemia of Grade = 1 c) Any Chemistry abnormality of Grade = 2 [except Grade 2 indirect bilirubin permitted if diagnosed Gilbert’s disease] 4) Pregnant Women and Women of Childbearing Potential (WOCBP) WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) and is not postmenopausal. Post menapause is defined as: • Amenorrhea = 12 consecutive months without another cause or • For women with irregular menstrual periods on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level = 35 mIU/mL). Women who are amenorrheic due to chemotherapy, who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be WOCBP. To be eligible, women must be postmenopausal based on age-related amenorrhea, surgical sterilization or ovarian suppression by use of goserelin (Zoladex®) or other LH-RH agonist, see Inclusion 5. 5) Allergies and Adverse Drug Reactions a) Extremely lactose intolerant, in the judgment of Treating Physician (100 mg dasatinib contains 135 mg lactose, posing a problem only if intolerance is severe) 6) Prohibited Treatments and/or Therapies [see Protocol Section 5.5.1] a) Is receiving any of the following concomitant medications: Category I drugs that are generally accepted to have a risk of causi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare progression-free survival (PFS) distribution for exemestane plus dasatinib vs exemestane plus placebo.;Secondary Objective: 1) To estimate Clinical Benefit Rate (CBR) and Freedom-From-Progression at 6 months (FFP-6) in each treatment arm; 2) To estimate [in subjects evaluable for response] the Objective Response Rate, Time to Response and Response Duration in each treatment arm; 3) To assess safety and tolerability in each treatment arm; 4) To evaluate [in subjects with bone metastasis] changes in subject-reported pain intensity and markers of bone lysis in each treatment arm.;Primary end point(s): The primary efficacy endpoint is Progression free survival (PFS). PFS will be defined as time from date of randomization until date PD is first reported. Subjects who die without a reported prior progression will be considered to have progressed on the day of their death. Subjects who initiate other non-study treatment for breast cancer (excluding palliative radiotherapy per Protocol Section 5.5.1) will be censored at the day of last tumor assessment prior to that other therapy. Subjects who neither progress nor die will be censored at the day of their last on-study tumor assessment, or initiation of subsequent therapy, whichever is later. Subjects who have no on-study tumor assessments will be censored on the day they were randomized. | — |
Countries
Czech Republic, France, Ireland, Italy, Spain, Sweden, United Kingdom
Outcome results
None listed