Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

Percentage of Participants Who Achieved a Best Response of Complete Response, Partial Response, and Stable Disease (CR+PR+SD) (Clinical Benefit Rate)
Clinical benefit rate is defined as the rate of confirmed CR, confirmed PR, and SD for 24 weeks duration and is the best response CR, PR, or SD as classified by the investigators according to the RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of not-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameter since treatment started. Kaplan-Meier (KM) techniques were used to assess the time-to-event endpoints. Progressive Disease (PD) was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir.
Baseline to Measured Progressive Disease or Study Discontinuation (Up to 24 Weeks)

Secondary Outcomes (5)

Percentage of Participants Achieving Overall Tumor Response Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR])
Baseline to Measured Progressive Disease or Study Discontinuation (Up to 24 Weeks)
Duration of Clinical Benefit
Time of Clinical Benefit to Progressive Disease or Death (Up to 3 Years)
Progression Free Survival (PFS)
Baseline to Measured Progressive Disease or Death Due to Any Cause (Up to 3 Years)
Number of Participants Who Discontinued With Adverse Events (AE) and Serious Adverse Events (SAEs)
From Baseline to Study Completion (Up to 3 years, 9 months)
Percentage of Participants With Enzastaurin Biomarkers and Disease State
Baseline, Cycle 2 to Study Completion (Up to 3 Years, 9 Months)

Study Arms (2)

Enzastaurin + Fulvestrant

EXPERIMENTAL

Participants received Enzastaurin loading dose of 1125 mg, on Day 1 of Cycle 1 only then received Enzastaurin 500 mg orally (QD) once daily in a 28-day cycle. Participants received enzastaurin loading dose of 1125 mg, on Day 1 of Cycle 1 only then received Enzastaurin 250 mg orally (BID) twice daily in a 28-day cycle. Fulvestrant was given intramuscularly at a loading dose of 500 mg on Day 1 and 250 mg on Day 15 in Cycle 1. Subsequent doses of Fulvestrant 250 mg were given on Day 1 of Cycle 2 and every 28 days thereafter.

Drug: enzastaurinDrug: fulvestrant

Fulvestrant + Placebo

PLACEBO COMPARATOR

Participants received fulvestrant: 500 mg, IM, day 1, 1250 mg, IM, day 15 cycle 1 then 250 mg, IM, every 28 days, until disease progression. Then, participants received placebo, oral, daily.

Drug: placeboDrug: fulvestrant

Interventions

enzastaurinDRUG

1125 milligram (mg) loading dose then 250 mg, oral, twice daily (for a total of 500 mg), until disease progression

Also known as: LY317615

Enzastaurin + Fulvestrant

placeboDRUG

oral, daily

Fulvestrant + Placebo

fulvestrantDRUG

500 mg, intramuscular (IM), day 1, 1250 mg, IM, day 15 cycle 1 then 250 mg, IM, every 28 days, until disease progression

Enzastaurin + FulvestrantFulvestrant + Placebo

Eligibility Criteria

Age18 Years+

Sexfemale

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Female participants with a histological-documented diagnosis of locally advanced or metastatic breast cancer. The primary or metastatic tumor must be estrogen response (ER) and/or parathyroid hormone receptor (PtR) positive.
Note: Hormone receptor positivity is defined as ER or PtR greater than 10 fmol/mg by biochemical assay or 10% positive cells by immunohistochemistry
Participants are resistant to aromatase inhibitors (AI) therapy
Females with postmenopausal status
Previous radiation therapy is allowed, but should have been limited
Measurable or non-measurable disease
Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) scale
Have adequate organ function
Have an estimated life expectancy of at least 24 weeks
Must sign an informed consent document

You may not qualify if:

Have had prior treatment with fulvestrant or enzastaurin
Are receiving concurrent administration of any other antitumor therapy, with the exception of gonadotropin-releasing hormone (GnRH) antagonists.
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
Have received supplemental estrogen or progesterone within 4 weeks prior to study entry
Are hormone estrogen receptor (HER2)-positive
Are unable to discontinue use of anticoagulants
Have hypercalcemia
Have a second primary malignancy that is clinically detectable at the time of consideration for study enrollment
Have documented central nervous system (CNS) metastases, symptomatic pulmonary lymphangitis, or involvement of more than 1/3 of the liver
Have a serious concomitant systemic disorder
Have a serious cardiac condition
Are unwilling or unable to discontinue use of carbamazepine, phenobarbital, or phenytoin at least 14 days prior to study therapy
Are unable to swallow tablets.

Contact the study team to confirm eligibility.