Enzastaurin Plus Fulvestrant vs. Placebo Plus Fulvestrant in Breast Cancer

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• Breast Neoplasms 12,544

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 156 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Lead sponsor

Eli Lilly and Company is the lead sponsor of 2,048 studies on the registry; 140 are open to participants now.

Of its 521 completed or terminated interventional studies of FDA-regulated products, 341 (65%) have results posted.

Study arms

• Experimental
  Enzastaurin + Fulvestrant

  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: enzastaurin · Drug: fulvestrant

• Placebo comparator
  Fulvestrant + Placebo

  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: placebo · Drug: fulvestrant

Interventions

• Drugenzastaurin

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

  Also known as: LY317615

• Drugplacebo

  oral, daily

• Drugfulvestrant

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

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.

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

Secondary outcomes

1. 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)

2. Duration of Clinical Benefit

   The duration of clinical benefit was measured from the time of clinical benefit of CR, PR or SD to the time of progressive disease or death from any cause. PD was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir. Kaplan-Meier (KM) techniques were used to assess the time-to-event endpoints.

   Time frame: Time of Clinical Benefit to Progressive Disease or Death (Up to 3 Years)

3. Progression Free Survival (PFS)

   Progression-free survival (PFS) time was defined as the time from baseline to the first date of progressive disease (symptomatic or objective) or death due to any cause, whichever occurred first. PD was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir.For participants who were not known to have died or progressed as of the data-inclusion cutoff date, PFS time was censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systematic anticancer therapy. PFS was summarized using Kaplan-Meier estimates.

   Time frame: Baseline to Measured Progressive Disease or Death Due to Any Cause (Up to 3 Years)

4. Number of Participants Who Discontinued With Adverse Events (AE) and Serious Adverse Events (SAEs)

   Clinically significant events were defined as serious AEs (SAEs) and other non-serious AEs, regardless of causality. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. Participants who discontinued due to an AE or SAE are reported.

   Time frame: From Baseline to Study Completion (Up to 3 years, 9 months)

5. Percentage of Participants With Enzastaurin Biomarkers and Disease State

   Time frame: Baseline, Cycle 2 to Study Completion (Up to 3 Years, 9 Months)

Baseline characteristics

Related links

• Lilly Clinical Trial Registry ↗

Individual participant data

Plan to share: Yes — Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Supporting information: Study protocol, Sap, Csr