Enzastaurin Plus Fulvestrant vs. Placebo Plus Fulvestrant in Breast Cancer

Eli Lilly and Company156 enrolled

Overview

The primary purpose of this study is to help answer the following research question: whether enzastaurin given together with fulvestrant can help participants who have breast cancer and make the tumor smaller or disappear and for how long.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

156

Conditions

Breast Cancer

Interventions

enzastaurinDRUG

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

placeboDRUG

oral, daily

fulvestrantDRUG

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

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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.

Locations (21)

Outcomes

Primary Outcomes

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.

Time frame: Baseline to Measured Progressive Disease or Study Discontinuation (Up to 24 Weeks)

Secondary Outcomes

Percentage of Participants Achieving Overall Tumor Response Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR])

The ORR is equal to the percentage of participants achieving a best overall response of partial response or complete response (PR + CR), according to RECIST version 1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes must have reduction in short axis to \<10 millimeter (mm) and normalization of tumor marker level of non-target lesions; PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions; PD was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir; SD was defined as small changes that did not meet above criteria. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. The 95% confidence interval (CI) was calculated by exact method. Kaplan-Meier (KM) techniques were used to assess the time-to-event endpoints.

Time frame: Baseline to Measured Progressive Disease or Study Discontinuation (Up to 24 Weeks)

Data from ClinicalTrials.gov

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Besançon, France

Paris, France

Saint-Herblain, France

Toulouse, France

Bielefeld, Germany

Dresden, Germany

Gütersloh, Germany

Kiel, Germany

Mannheim, Germany

Meldola, Italy

...and 11 more locations