Breast Cancer
Conditions
Keywords
Metastatic
Brief summary
The primary purpose of this study is to determine the objective response rate (complete and partial response) for patients who receive LY573636-sodium for metastatic breast cancer.
Detailed description
Patient will receive a 2-hour intravenous infusion of study drug (LY573636-sodium) once every 28 days. Radiologic imaging scans will be performed before the first dose of study drug and then after every other treatment. Patients will be assessed for clinical progression at every visit and for response approximately every 56 days (every other cycle).
Interventions
DRUGLY573636-sodium
Dose is adjusted to target a specific maximum concentration (Cmax) based on patient laboratory parameters, administered intravenously every 28 days until disease progression or other criteria for patient discontinuation are met
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Received at least 2 or more prior chemotherapy regimens for metastatic breast cancer. * Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 4 weeks. Patients who have received whole-brain radiation must wait 90 days.
Exclusion criteria
* Serious pre-existing medical condition. * Have active central nervous system or leptomeningeal metastasis. * Current hematologic malignancies, acute or chronic leukemia. * Receiving Warfarin (Coumadin). * Have a history of radiation therapy involving more than 25% of the bone marrow.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Objective Overall Response | Baseline to measured progressive disease or death from any cause up to 12 months | Objective overall response is complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. It is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing Clinical Benefit [(CR) + (PR) + Stable Disease (SD)] | Baseline to measured progressive disease or death from any cause up to 12 months | Clinical Benefit Rate = \[(CR) + (PR) + Stable Disease (SD)\] of at least 4 cycles/N as classified by the investigator according to the RECIST guidelines, where N = total number of participants with at least one dose of study drug. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. |
| Duration of Overall Response | Time of response to progressive disease or death up to 12 months | The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. CR or PR is classified by the investigators according to RECIST guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. |
| Progression-free Survival | Baseline to measured progressive disease or death from any cause up to 12 months | Defined as the time from date of first dose to the first observation of progression of disease (PD) or death due to any cause. PD was determined using RECIST criteria. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. |
| The Percentage of Participants With Exposures in the Target Range | After drug infusion in cycles 1 and 2 (5 samples drawn over each 28 day cycle) | Exposure is the amount of drug the body sees in a period of time. Target range is an exposure thought to offer the optimal balance of safety and efficacy based on prior research. |
| Maximum Concentration (Cmax) | After drug infusion in cycles 1 and 2 (5 samples drawn over each 28 day cycle)] | — |
| Duration of Stable Disease | Time from documented Stable Disease (SD) to first date of progressive disease or death from any cause up to 12 months | Duration of stable disease (SD) is defined from date of documented SD to first date of progressive disease (PD) or death from any cause (assessed every other cycle during study therapy, or every 2 months during post-therapy). SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PR is ≥30% decrease in sum of longest diameter of target lesions. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LY573636-sodium Dose was adjusted to target a specific maximum concentration (Cmax) based on patient laboratory parameters, administered intravenously every 28 days until disease progression or other criteria for patient discontinuation were met | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Entry Criteria Not Met | 8 |
Baseline characteristics
| Characteristic | LY573636-sodium |
|---|---|
| Age, Continuous | 55.43 years STANDARD_DEVIATION 9.71 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - Fully active | 10 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 - Ambulatory, restricted strenuous activity | 23 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants |
| Race/Ethnicity, Customized White | 29 Participants |
| Region of Enrollment United States | 33 Participants |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 32 / 33 |
| serious Total, serious adverse events | 10 / 33 |
Outcome results
Primary
Percentage of Participants With an Objective Overall Response
Objective overall response is complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. It is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100.
Time frame: Baseline to measured progressive disease or death from any cause up to 12 months
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY573636-sodium | Percentage of Participants With an Objective Overall Response | 6.1 percentage of participants |
Secondary
Duration of Overall Response
The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. CR or PR is classified by the investigators according to RECIST guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions.
Time frame: Time of response to progressive disease or death up to 12 months
Population: Zero participants analyzed. Duration of Overall Response for CR and PR data was not collected for analysis.
Secondary
Duration of Stable Disease
Duration of stable disease (SD) is defined from date of documented SD to first date of progressive disease (PD) or death from any cause (assessed every other cycle during study therapy, or every 2 months during post-therapy). SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PR is ≥30% decrease in sum of longest diameter of target lesions. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion.
Time frame: Time from documented Stable Disease (SD) to first date of progressive disease or death from any cause up to 12 months
Population: All participants who received at least one dose of the study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY573636-sodium | Duration of Stable Disease | 3.52 months |
Secondary
Maximum Concentration (Cmax)
Time frame: After drug infusion in cycles 1 and 2 (5 samples drawn over each 28 day cycle)]
Population: All participants who received at least one dose of the study drug.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY573636-sodium | Maximum Concentration (Cmax) | Cycle 1 | 375 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 16.4 |
| LY573636-sodium | Maximum Concentration (Cmax) | Cycle 2 | 339 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 17.2 |
Secondary
Percentage of Participants Experiencing Clinical Benefit [(CR) + (PR) + Stable Disease (SD)]
Clinical Benefit Rate = \[(CR) + (PR) + Stable Disease (SD)\] of at least 4 cycles/N as classified by the investigator according to the RECIST guidelines, where N = total number of participants with at least one dose of study drug. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.
Time frame: Baseline to measured progressive disease or death from any cause up to 12 months
Population: All participants who received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY573636-sodium | Percentage of Participants Experiencing Clinical Benefit [(CR) + (PR) + Stable Disease (SD)] | 9.1 percentage of participants |
Secondary
Progression-free Survival
Defined as the time from date of first dose to the first observation of progression of disease (PD) or death due to any cause. PD was determined using RECIST criteria. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion.
Time frame: Baseline to measured progressive disease or death from any cause up to 12 months
Population: All participants who received at least 1 dose of the study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY573636-sodium | Progression-free Survival | 1.81 months |
Secondary
The Percentage of Participants With Exposures in the Target Range
Exposure is the amount of drug the body sees in a period of time. Target range is an exposure thought to offer the optimal balance of safety and efficacy based on prior research.
Time frame: After drug infusion in cycles 1 and 2 (5 samples drawn over each 28 day cycle)
Population: All participants who received at least one dose of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY573636-sodium | The Percentage of Participants With Exposures in the Target Range | Cycle 1 | 45 Percentage of participants |
| LY573636-sodium | The Percentage of Participants With Exposures in the Target Range | Cycle 2 | 52 Percentage of participants |