Enzastaurin Plus Fulvestrant vs. Placebo Plus Fulvestrant in Breast Cancer

Lilly

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Drug: enzastaurin; Drug: fulvestrant; Drug: placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00451555

10736

H6Q-MC-S023 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 156 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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156 participants in 2 patient groups, including a placebo group

Enzastaurin + Fulvestrant

Experimental group

Description:

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.

Treatment:

Drug: fulvestrant

Drug: enzastaurin

Fulvestrant + Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: fulvestrant

Drug: placebo