Sarcoma, Soft Tissue
Conditions
Brief summary
The primary purpose of the study is to estimate the time from the first dose of LY573636-sodium (hereafter referred to as LY573636) to the date your physician determines that your disease has progressed or worsened.
Detailed description
Patients will receive a 2-hour intravenous infusion of study drug (LY573636) once every 21 days or 28 days depending on their target dose. Radiological 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 42 days or 56 days (every other cycle).
Interventions
DRUGLY573636-sodium
LY573636 dose is dependent on patient's height, weight, and gender to target a specific maximum concentration (Cmax). LY573636 is administered intravenously every 21 or 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
* Diagnosis of soft tissue sarcoma that is unresectable or metastatic * Have received one or two (but no more than two) prior treatment regimens for metastatic soft tissue sarcoma, one of which must have included doxorubicin (adriamycin). * Must have stopped all previous treatments for cancer, including chemotherapy, radiation therapy or other investigational treatments for cancer for at least 30 days
Exclusion criteria
* Participants with primary bone sarcoma (for example osteosarcoma, Ewing's sarcoma, chondrosarcoma), gastrointestinal stromal tumor (GIST) and Kaposi's sarcoma * Serious pre-existing medical problems (as determined by your doctor) * Have received more than two previous systemic treatment regimens for unresectable or metastatic soft tissue sarcoma * Have a second primary cancer (unless cancer-free for more than 2 years) * Active treatment with Warfarin (Coumadin)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | First treatment dose to measured progressive disease or death from any cause up to 15.57 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 the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.0). PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Clinical Benefit Rate) | First treatment dose to measured progressive disease or death due to any cause up to 15.57 months | Clinical Benefit Rate = (CR + PR + SD)/N as classified according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines (version 1.0), 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. |
| Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 | Predose up to 2 hours postdose in Cycles 1 and 2 (21- or 28-day cycle) | — |
| Overall Survival Time | First treatment dose to death due to any cause up to 26.51 months | Defined as the time from date of first dose to the date of death due to any cause. |
| Percentage of Participants With Complete Response or Partial Response (Objective Response Rate) | First treatment dose to measured progressive disease or death due to any cause up to 15.57 months | Objective response rate is the percentage of participants with complete response (CR) or partial response (PR), as assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines (version 1.0). CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. Objective response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100. |
| Duration of Stable Disease (SD) | Time from documented SD or better to first date of progressive disease up to 15.57 months | Duration of SD is defined from date of documented SD or better to first date of progression of disease (PD) (assessed every other cycle during study therapy, or every 2 months during post-therapy until PD). SD is neither sufficient shrinkage to qualify for partial response (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. |
| Number of Participants With Adverse Events (Safety) | First treatment dose up to 26.51 months | Data are presented as number of participants who experienced serious adverse events or all other nonserious adverse events during the study. A summary of serious adverse events and other nonserious adverse events is located in the Reported Adverse Event section. |
| Duration of Overall Objective Response | Time of response to progressive disease or death up to 15.57 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 of disease or death due to any cause. CR or PR is classified according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines (version 1.0). CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. |
Countries
Argentina, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LY573636 Target Cmax 420 µg/mL LY573636 dose is dependent on participant's height, weight, and gender to target maximum concentration (Cmax) of 420 micrograms/milliliter (µg/mL) and is administered intravenously every 21- or 28-day cycle until disease progression or other criteria for participant discontinuation are met. | 63 |
| LY573636 Target Cmax 360 µg/mL LY573636 dose is dependent on participant's height, weight, and gender to target maximum concentration (Cmax) of 360 micrograms/milliliter (µg/mL) and is administered intravenously every 21- or 28-day cycle until disease progression or other criteria for participant discontinuation are met. | 38 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | Death | 3 | 1 |
| Overall Study | Investigator Decision | 1 | 0 |
| Overall Study | Progressive Disease | 53 | 34 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | LY573636 Target Cmax 420 µg/mL | LY573636 Target Cmax 360 µg/mL | Total |
|---|---|---|---|
| Age, Continuous | 53.8 years STANDARD_DEVIATION 15.29 | 52.6 years STANDARD_DEVIATION 13.57 | 53.3 years STANDARD_DEVIATION 14.61 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - Fully active | 30 Participants | 18 Participants | 48 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 - Ambulatory, restricted strenuous activity | 33 Participants | 19 Participants | 52 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Unknown | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized African | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Caucasian | 54 Participants | 29 Participants | 83 Participants |
| Race/Ethnicity, Customized East Asian | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic | 6 Participants | 5 Participants | 11 Participants |
| Region of Enrollment Argentina | 11 Participants | 4 Participants | 15 Participants |
| Region of Enrollment Spain | 9 Participants | 4 Participants | 13 Participants |
| Region of Enrollment United States | 43 Participants | 30 Participants | 73 Participants |
| Sex: Female, Male Female | 30 Participants | 21 Participants | 51 Participants |
| Sex: Female, Male Male | 33 Participants | 17 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 59 / 63 | 36 / 38 |
| serious Total, serious adverse events | 23 / 63 | 10 / 38 |
Outcome results
Primary
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 the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.0). PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion.
Time frame: First treatment dose to measured progressive disease or death from any cause up to 15.57 months
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY573636 Target Cmax 420 µg/mL | Progression-Free Survival | 2.64 months |
| LY573636 Target Cmax 360 µg/mL | Progression-Free Survival | 1.38 months |
Secondary
Duration of Overall Objective 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 of disease or death due to any cause. CR or PR is classified according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines (version 1.0). 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 15.57 months
Population: Zero participants analyzed. Duration of Response for CR and PR data was not collected for analysis due to N=0 CR and N=3 PR.
Secondary
Duration of Stable Disease (SD)
Duration of SD is defined from date of documented SD or better to first date of progression of disease (PD) (assessed every other cycle during study therapy, or every 2 months during post-therapy until PD). SD is neither sufficient shrinkage to qualify for partial response (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 SD or better to first date of progressive disease up to 15.57 months
Population: All enrolled participants who received at least 1 dose of study drug and had a best overall response of stable disease or better.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY573636 Target Cmax 420 µg/mL | Duration of Stable Disease (SD) | 4.44 months |
| LY573636 Target Cmax 360 µg/mL | Duration of Stable Disease (SD) | 5.91 months |
Secondary
Number of Participants With Adverse Events (Safety)
Data are presented as number of participants who experienced serious adverse events or all other nonserious adverse events during the study. A summary of serious adverse events and other nonserious adverse events is located in the Reported Adverse Event section.
Time frame: First treatment dose up to 26.51 months
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LY573636 Target Cmax 420 µg/mL | Number of Participants With Adverse Events (Safety) | Serious Adverse Events | 23 Participants |
| LY573636 Target Cmax 420 µg/mL | Number of Participants With Adverse Events (Safety) | Other Nonserious Adverse Events | 59 Participants |
| LY573636 Target Cmax 360 µg/mL | Number of Participants With Adverse Events (Safety) | Serious Adverse Events | 10 Participants |
| LY573636 Target Cmax 360 µg/mL | Number of Participants With Adverse Events (Safety) | Other Nonserious Adverse Events | 36 Participants |
Secondary
Overall Survival Time
Defined as the time from date of first dose to the date of death due to any cause.
Time frame: First treatment dose to death due to any cause up to 26.51 months
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY573636 Target Cmax 420 µg/mL | Overall Survival Time | 8.71 months |
| LY573636 Target Cmax 360 µg/mL | Overall Survival Time | 12.25 months |
Secondary
Percentage of Participants With Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Clinical Benefit Rate)
Clinical Benefit Rate = (CR + PR + SD)/N as classified according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines (version 1.0), 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: First treatment dose to measured progressive disease or death due to any cause up to 15.57 months
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY573636 Target Cmax 420 µg/mL | Percentage of Participants With Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Clinical Benefit Rate) | 46.0 percentage of participants |
| LY573636 Target Cmax 360 µg/mL | Percentage of Participants With Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Clinical Benefit Rate) | 26.3 percentage of participants |
Secondary
Percentage of Participants With Complete Response or Partial Response (Objective Response Rate)
Objective response rate is the percentage of participants with complete response (CR) or partial response (PR), as assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines (version 1.0). CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. Objective response rate 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: First treatment dose to measured progressive disease or death due to any cause up to 15.57 months
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY573636 Target Cmax 420 µg/mL | Percentage of Participants With Complete Response or Partial Response (Objective Response Rate) | Complete Response (CR) | 0.0 percentage of participants |
| LY573636 Target Cmax 420 µg/mL | Percentage of Participants With Complete Response or Partial Response (Objective Response Rate) | Partial Response (PR) | 3.2 percentage of participants |
| LY573636 Target Cmax 360 µg/mL | Percentage of Participants With Complete Response or Partial Response (Objective Response Rate) | Complete Response (CR) | 0.0 percentage of participants |
| LY573636 Target Cmax 360 µg/mL | Percentage of Participants With Complete Response or Partial Response (Objective Response Rate) | Partial Response (PR) | 2.6 percentage of participants |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of LY573636
Time frame: Predose up to 2 hours postdose in Cycles 1 and 2 (21- or 28-day cycle)
Population: Participants who received study drug and had pharmacokinetic (PK) data at the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY573636 Target Cmax 420 µg/mL | Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 | Cycle 1 | 386.0 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 14 |
| LY573636 Target Cmax 420 µg/mL | Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 | Cycle 2 | 346.5 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 15 |
| LY573636 Target Cmax 360 µg/mL | Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 | Cycle 1 | 325.7 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 14.5 |
| LY573636 Target Cmax 360 µg/mL | Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 | Cycle 2 | 351.8 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 12.8 |