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: Patients will be included from the study if they meet all of the following 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 PR receptor positive. [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. [3] Females with postmenopausal status defined as: • Age = 60 years or age = 45 years and 24 months from the last menstrual period with intact uterus • Follicle-stimulating hormone level within postmenopausal range • Prior radiation, medical or surgical castration (such as bilateral salpingo-oophorectomy) [4] Previous radiation therapy is allowed, but should have been limited and must not have included whole pelvis radiation. Patients must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia). Lesions that have been irradiated cannot be included as sites of measurable disease unless clear tumor progression, according to RECIST criteria, has been documented in these lesions since the end of radiation therapy [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). (Note: The number of patients with evaluable-only (nonmeasurable, for example bone metastases) disease to be enrolled in the trial will be limited to a maximum of 40 p
Exclusion criteria
Exclusion criteria: Patients will be excluded from the study if they meet any of the following 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 [15] Exclusion Criterion [15] has been deleted [16] Are receiving concurrent administration of any other antitumor therapy, with the exception of gonadotropin-releasing hormone (GnRH) antagonists. [17] Have received treatment within the last 4 weeks with a drug that has not received regulatory approval for any indication at the time of study entry [18] Have received supplemental estrogen or progesterone within 4 weeks prior to study entry [19] Are HER2-positive [20] Are unable to discontinue use of anticoagulants [21] Have hypercalcemia: corrected calcium >10% over ULN [22] Have a second primary malignancy that is clinically detectable at the time of consideration for study enrollment [23] Have documented central nervous system (CNS) metastases, symptomatic pulmonary lymphangitis, or involvement of more than 1/3 of the liver (that is, patients with rapidly progressive disease, or those whose assessment dictates that chemotherapy would be more appropriate) [24] Have a serious concomitant systemic disorder (for example, active infection including HIV) incompatible with the study (at the discretion of investigator), previous history of bleeding diathesis, or coagulation treatment [25] Have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV (Bruce RA 1956) [26] Are unwilling or unable to discontinue use of carbamazepine, phenobarbital, or phenytoin at least 14 days prior to study therapy [27] Are unable to swallow tablets. [28] Exclusion Criterion [28] has been deleted [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: o 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 o to compare the following endpoints between the randomized treatment arms 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: o response rates (RR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines o duration of clinical benefit o progression-free survival (PFS) o safety and adverse event profile using Common Terminology Criteria for Adverse Events o 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