Enzastaurin in Combination of Capecitabine to Treat Breast Cancer

Phase 2TerminatedNCT00437294

Eli Lilly and Company86 enrolled

Overview

The purpose of this study is to determine whether the combination of enzastaurin and capecitabine is more effective than the combination of placebo and capecitabine in treating participants with breast cancer who were previously treated with an anthracycline and a taxane.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Breast Cancer

Interventions

enzastaurinDRUG

1125 milligrams (mg) loading dose then 500 mg, oral, daily, 21-day cycles until progressive disease

placeboDRUG

oral, daily, 21-day cycles until progressive disease

capecitabineDRUG

1250 mg/m\^2, BID, days 1-14 of each 21-day cycle until progressive disease

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Have been diagnosed with metastatic or recurrent breast cancer. * Have been previously treated with both an anthracycline and a taxane. * Have not received more than two prior chemotherapy treatment programs. * Have stopped any antitumoral hormonal treatment before you enroll in this study. * Have a negative pregnancy blood test if menstruating or capable of becoming pregnant. You must use an approved birth control method during the study and for 3 months after stopping study treatment. Exclusion Criteria: * Cannot follow the study procedures (for example, you cannot swallow tablets). * Are receiving another treatment for your cancer. * Have received another experimental drug in the last 4 weeks. * Have had serious heart disease within last 6 months. * Are pregnant or breast-feeding.

Locations (20)

Outcomes

Primary Outcomes

Progression Free Survival (PFS)

PFS was defined as the time from randomization to the first observation of disease progression or death due to any cause. For participants not known to have died as of the data cut-off date and who did not have progressive disease, PFS was censored at the date of last visit with adequate assessment. For participants who received subsequent anticancer therapy (after discontinuation from the study treatment) prior to disease progression or death, PFS was censored at the date of last visit with adequate assessment prior to the initiation of post-discontinuation anticancer therapy.

Time frame: Randomization to measured progressive disease or death up to 14 months

Secondary Outcomes

Expression of Tumor Markers in Tissue Samples (Tumor Markers and Genes Evaluation)

Protein expression was planned to be measured using an Immunohistochemistry (IHC) assay to determine membrane and cytoplasmic phosphorylated glycogen synthase kinase 3 beta (pGSK3B), nuclear phosphorylated adenosine 3'5'-cyclic monophosphate (cAMP) response-element binding protein (pCREB), cytoplasmic pCREB, protein kinase C beta 2 (PKCB2), cytoplasmic phospho S6 (pS6), and cytoplasmic phosphatase and tensin homolog (PTEN) IHC H-scores. Tumor tissue samples were to be scored using a 0 (negative, no staining) to 3+ (brightest staining) scoring system for cytoplasmic and nuclear staining, and H- scores calculated using formula: 1x(percentage of cells stained 1+) + 2x(percentage of cells stained 2+) + 3x(percentage of cells stained 3+) .

Time frame: Randomization, Cycle 2, end of study

Pharmacokinetics: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State

Area Under the Concentration versus time curve during 1 dosing interval at steady state (AUCτ,ss) for Cycle 2 Day 1 for Enzastaurin, its metabolite LY326020 and total analytes (enzastaurin + LY326020). AUCτ,ss was calculated using concentration versus time data by post hoc estimation of enzastaurin, its metabolite LY326020, and total analytes (enzastaurin + LY326020).

Time frame: From pre-dose to 24 hours post-dose on Day 1 of Cycle 2

Data from ClinicalTrials.gov

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Buenos Aires, Argentina

Resistencia, Argentina

Tucumain, Argentina

Garran, Australian Capital Territory, Australia

Caringbah, New South Wales, Australia

Wollongong, New South Wales, Australia

Frankston, Victoria, Australia

Nedlands, Western Australia, Australia

Subiaco, Western Australia, Australia

Avignon, France

...and 10 more locations

Duration of Response (DOR)

The DOR was defined as the time from first objective status assessment of complete response (CR) or partial response (PR) to the first time of progression or death as a result of any cause. According to the Response Evaluation Criteria in Solid Tumors (RECIST V1.0) criteria, CR was the disappearance of all tumor lesions. PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions or complete disappearance of target lesions, with persistence (but not worsening) of 1 or more non-target lesions, with occurrence of no new lesions. For participants not known to have died as of the data cut-off date and who did not have progressive disease, DOR was censored at the date of last visit with adequate assessment. For participants who received subsequent anticancer therapy (after discontinuation from the study treatment) prior to disease progression or death, DOR was censored at the date of last visit with adequate assessment.

Time frame: Randomization to last visit (up to 9.66 months)