A Study of LY2523355 in Participants With Breast Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to evaluate the anti-tumor activity of LY2523355 relative to ixabepilone for the treatment of metastatic or locally recurrent breast cancer using change in tumor size as a continuous measure of response.

Official Title
-----------------
A Randomized Phase 2 Study of LY2523355 Versus Ixabepilone in Patients With Metastatic or Locally Recurrent Breast Cancer Who Have Received Prior Taxane Therapy

Conditions
-----------------
Metastatic Breast Cancer

Intervention / Treatment
-----------------
* Drug: LY2523355
* Drug: ixabepilone
* Drug: pegfilgrastim
* Drug: filgrastim


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have histologic or cytologic diagnosis of metastatic or locally recurrent breast cancer that is not amenable to therapy given with curative intent. Have measurable disease defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 guidelines. Have received 2 or more prior standard cytotoxic chemotherapy regimens for metastatic breast cancer and be, in the opinion of the investigator, an appropriate candidate for experimental therapy. Regimens received in the neoadjuvant or adjuvant setting are not counted as prior regimens. Have received a prior taxane in the neoadjuvant, adjuvant, or metastatic setting. Have recovered from the acute effects of prior chemotherapy, hormonal therapy, and radiation prior to study enrollment. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale. Have adequate organ function. Exclusion Criteria: Have Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater (moderate or worse) peripheral neuropathy Have a second primary malignancy. Have symptomatic, untreated, or uncontrolled central nervous system metastases. Have received autologous stem cell transplant following high-dose chemotherapy. Have serious preexisting medical conditions that in the opinion of the investigator would preclude participation in this study. Have active symptomatic fungal, bacterial, and/or known viral infection including active human immunodeficiency virus (HIV) or viral hepatitis. Have previously received LY2523355 in another study investigating this agent or therapy with ixabepilone or an ixabepilone-containing regimen. Have a history of radiation therapy involving more than 25 percent of the bone marrow. Have a Fridericia corrected QT (QTcF) interval of >470 milliseconds (msec) on screening electrocardiogram (ECG). Have QRS widening of >120 msec on screening ECG. Cannot change or stop taking a strong Cytochrome P450 3A4 (CYP3A4) inhibitor or CYP3A4 inducer per the ixabepilone label. Have hypersensitivity to drugs formulated with Cremophor® EL per the ixabepilone label.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2523355 + pegfilgrastim or filgrastim<br>LY2523355: Five milligrams per meter squared per day (mg/m^2/day) (dosage determined by calculating participant's body surface area) administered intravenously as a 1-hour infusion on Days 1, 2, and 3 of a 21-day Cycle for 2 Cycles. Pegfilgrastim or Filgrastim: Dosage is determined by standard of care and is administered intravenously on Day 4 of 21-day Cycle for 2 Cycles. If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met. | Drug: LY2523355<br>* Administered intravenously as a one hour infusion<br>Drug: pegfilgrastim<br>* Administered intravenously<br>Drug: filgrastim<br>* Administered intravenously<br>|
| Active Comparator: ixabepilone<br>Forty milligrams per meter squared per day (mg/m^2/day) (dosage determined by calculating participant's body surface area) administered intravenously as a 3-hour infusion on Day 1 of a 21-day Cycle for 2 Cycles. If at the end of 2 Cycles the participant was receiving benefit, the participant may have remained on study drug for additional cycles until a criterion for study discontinuation was met. | Drug: ixabepilone<br>* Administered intravenously<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Tumor Size (CTS) From Baseline to the End of Cycle 2 | The log ratio of tumor size at Cycle 2 to tumor size at baseline is calculated for each participant, where the tumor size is the sum of the target lesion measurements at each assessment. | Baseline up to end of Cycle 2 (Day 42) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving an Overall Response (Overall Response Rate) | Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guidelines. CR is a disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 millimeters (mm). PR is an at least 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with measurable disease, multiplied by 100. | Baseline to measured progressive disease or date of death from any cause (up to 423 days) | 
| Progression-free Survival (PFS) | Progression-free survival (PFS) is the time from the date of randomization to the first date of progressive disease (PD) or death due to any cause, whichever occurs first. PD is as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guidelines, and is defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if that was the smallest on study). In addition, the sum must have demonstrated an absolute increase of at least 5 millimeter (mm) (the appearance of 1 or more new lesions was considered progression). Kaplan-Meier analysis was performed on the observed distribution of PFS. Participants were censored from analysis for the following reasons: lack of disease assessment, lost to follow-up, and further anticancer therapy started. Median PFS is presented. | Baseline to measured progressive disease or date of death from any cause (up to 423 days) | 
| Percentage of Participants Achieving a Clinical Benefit (Clinical Benefit Rate) | Clinical benefit rate is the proportion of participants who achieve a best response of complete response (CR), partial response (PR), or stable disease (SD) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guidelines. CR is a disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 millimeters (mm). PR is an at least 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. SD is neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as progressive disease, taking as reference the smallest sum diameter since treatment started. Clinical benefit rate is calculated as a total number of participants with CR, PR, or SD divided by the total number of participants with measurable disease, multiplied by 100. | Baseline to measured progressive disease or date of death from any cause (up to 423 days) | 
| Pharmacokinetics, Maximum Plasma Concentration (Cmax) of LY2523355 | Cmax is the maximum plasma concentration of LY2523355 after a 1-hour intravenous infusion of LY2523355 on Day 1 and Day 3 of Cycle 1. | Cycle 1: Day 1 and Day 3 | 
| Pharmacokinetics, Maximum Plasma Concentration (Cmax) of LSN2546307 | Cmax is the maximum plasma concentration of LSN2546307 (metabolite) after a 1-hour intravenous infusion of LY2523355 on Day 1 and Day 3 of Cycle 1. | Cycle 1: Day 1 and Day 3 | 
| Pharmacokinetics, Intracycle Accumulation Ration (Ra) of LY2523355 | The intracycle accumulation ratio (Ra) is defined as the LY2523355 Cmax on Day 3 of Cycle 1 to the LY2523355 Cmax on Day 1 of Cycle 1 after a 1-hour intravenous infusion of LY2523355 on Day 1 and Day 3 of Cycle 1. | Cycle 1: Day 1 and Day 3 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Locally, Recurrent, Breast, Cancer