metastatic breast cancer, resistant to aromatase inhibitors MedDRA version: 8.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer
Conditions
Sponsors
Eli Lilly and Company limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] Female patients with a histological-documented diagnosis of locally advanced or metastatic breast cancer. The primary or metastatic tumor must be ER and/or PtR receptor positive. Note: Hormone receptor positivity is defined as ER or PtR >10 fmol/mg by biochemical assay or ?10% positive cells by immunohistochemistry [2] Patients are resistant to AI therapy • AI was administered in the adjuvant setting: patient should have been on treatment for at least 1 year and have had an objective recurrence during this treatment or in the first year after finishing it • AI was administered in advanced disease: ? If patients have not received previous chemotherapy for MBC, they must have achieved a tumor response or stabilization lasting at least 6 months and have had an objective progression during treatment ? If patients have received previous chemotherapy for MBC, they can have 3 different situations : • Chemotherapy ? AI (as maintenance of response). They must have received the AI lasting at least 6 months and have had an objective progression during treatment • Chemotherapy ? AI (at progression). They must have achieved a tumor response or stabilization lasting at least 6 months and have had an objective progression during treatment • AI ? Chemotherapy. They must have achieved a tumor response or stabilization to the AI and have had an objective progression after chemotherapy. [5] Measurable or nonmeasurable disease defined by: • At least 1 unidimensionally measurable lesion meeting RECIST (Protocol Attachment S023.5; Therasse et al. 2000) Guidelines. Positron emission tomography (PET) scans and ultrasounds may not be used • At least 1 nonmeasurable lesion whose presence is assessable using standard techniques or a spiral CT scan even though the lesion is smaller than the minimum size required for measurability (PET scans and ultrasounds may not be used). Patients with bone lesion(s) in the absence of measurable disease can be recruited provided they can be evaluated by X-ray, CT or MRI (patients with lesions assessed only by bone scan cannot be included) 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: [13] Have received treatment with more than 1 line of hormonal therapy in the metastatic setting [14] Have had prior treatment with fulvestrant, or enzastaurin [30] Patients with osteoporosis, defined as bone mineral density (BMD) T score <2.5 SD (standard deviation) or receiving treatment for osteoporosis. Note: Patients with BMD T score between 1 to 2.5 are defined as osteopenia, which, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient’s ability to complete the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Main objective : To compare the clinical benefit rate between fulvestrant plus enzastaurin and fulvestrant plus placebo in Aromatase Inhibitor resistant MBC. ; Secondary Objective: Secondary objectives: • to compare the clinical benefit rate between 2 pairs of patient cohorts: (1) fulvestrant plus enzastaurin BID and fulvestrant plus placebo; (2) fulvestrant plus enzastaurin QD and fulvestrant plus placebo • to compare the following endpoints between 3 pairs of patient cohorts: (1) all fulvestrant plus enzastaurin patients (BID+QD) and fulvestrant plus placebo; (2) fulvestrant plus enzastaurin BID and fulvestrant plus placebo; (3) fulvestrant plus enzastaurin QD and fulvestrant plus placebo: ? response rates (RR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines ? duration of clinical benefit ? progression-free survival (PFS) ? safety and adverse event profile in both treatment arms using Common Terminology Criteria for Adverse Events . • to assess biomarkers relevant to enzastaurin and the disease state, as well as their correlation to clinical outcome. ;Primary end point(s): The primary efficacy measure is the clinical benefit rate. Clinical benefit (CB) is defined as the best response of CR, PR, and SD for ?24 weeks duration. The CB rate is defined, for each treatment arm, as the number of patients with the best response of CR, PR, and SD for ?24 weeks duration divided by the number of randomized and treated patients. | — |
Countries
France, Germany, Italy, Netherlands, Spain
Outcome results
None listed