Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cancer
Conditions
Brief summary
The primary objective is to determine whether LY573636-sodium (hereafter referred to as LY573636) is effective in treating platinum-resistant ovarian cancer. Patients will receive an intravenous infusion of study drug once every 28 days. Computed tomography (CT) scans and CA-125 tests will be done before the first dose and then after every other treatment.
Interventions
DRUGLY573636-sodium
LY573636 dose is dependent on participant's height, weight, and gender and is adjusted to target a specific maximum concentration (Cmax) based on participant laboratory parameters. LY573636 is administered every 28 days until disease progression or other criteria for participant discontinuation are met.
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer * At least 18 years old * Have received at least one but no more than 2 systemic treatment regimens containing platinum (does not include regimens received before surgery for this cancer) * Have platinum-resistant disease
Exclusion criteria
* Have received more than 2 systemic treatment regimens for platinum-resistant disease * Serious pre-existing medical conditions * Actively receiving warfarin (Coumadin) for treatment of venous thrombosis or other prothrombotic conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Response and Partial Response (Objective Response Rate) | Baseline to measured progressive disease up to 12.68 months | Objective 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. 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Baseline to measured progressive disease or death due to any cause up to 21.26 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 Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. |
| Percentage of Participants With Complete Response, Partial Response, and Stable Disease (Clinical Benefit Rate) | Baseline to measured progressive disease up to 21.26 months | Clinical Benefit Rate is complete response (CR) + partial response (PR) + stable disease (SD) as classified by the investigator 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. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Clinical benefit rate is calculated as a total number of participants with CR or PR or SD divided by the total number of participants treated multiplied by 100. |
| Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 | Predose up to 2 hours postdose in Cycles 1 and 2 | — |
| Overall Survival | First treatment to death due to any cause up to 42.91 months | Overall survival is defined as the time from date of first treatment to the date of death due to any cause. For participants who were alive, overall survival was censored at their last contact. |
| Duration of Response | Time of response to time of measured progressive disease up to 12.68 months | The duration of response (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 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. |
| Duration of Stable Disease | Time from documented SD or better to first date of progressive disease or death due to any cause up to 21.26 months | Duration of stable disease is defined from date of documented stable disease (SD) or better to first date of progressive disease or death from any cause (assessed every cycle during study therapy, or every 2 months during post-therapy until disease progression or death). 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 43.91 months | Data are presented as number of participants who experienced serious adverse events or all other nonserious adverse events during the study including the 30-day follow-up period. A summary of serious adverse events and other nonserious adverse events is located in the Reported Adverse Event section. |
Other
| Measure | Time frame |
|---|---|
| Number of Participants Who Died Due to Progressive Disease During the 30 Days Following Discontinuation From Study Treatment | Study treatment discontinuation up to 30 days post study treatment discontinuation |
Countries
Italy, Russia, United States
Participant flow
Pre-assignment details
The reasons for discontinuation listed in the participant flow are the reasons the participant discontinued treatment and a participant was considered to have completed the trial if they experienced progressive disease or an adverse event.
Participants by arm
| Arm | Count |
|---|---|
| Target Cmax 420 µg/mL Loading dose of LY573636, targeting a maximum concentration (Cmax) of 420 micrograms/milliliter (μg/mL), followed by a lower chronic dose (which was 75% of the loading dose) in subsequent cycles, administered as an intravenous infusion given over approximately 2 hours, on Day 1 of a 21-day treatment cycle. | 53 |
| Target Cmax 360 μg/mL Loading dose of LY573636, targeting a Cmax of 360 μg/mL, followed by a lower chronic dose (which was 90% of the loading dose) in subsequent cycles, administered as an intravenous infusion given over approximately 2 hours, on Day 1 of a 21-day treatment cycle. | 18 |
| Albumin-Tailored Dose The dose of LY573636 administered in each infusion was based on participant's height, weight, gender, pre-cycle albumin level, and cycle number to target area under the curve above the albumin corrected threshold (AUCalb) in the range of 1200 to 6400 hour\*micrograms/milliliter (h\*μg/mL), administered over approximately 2 hours on Day 1 of a 28-day treatment cycle. | 32 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 2 |
| Overall Study | Death Due to Adverse Event | 3 | 0 | 5 |
| Overall Study | Death Due to Progressive Disease | 0 | 0 | 2 |
| Overall Study | Investigator Decision | 2 | 1 | 1 |
| Overall Study | Progressive Disease | 42 | 14 | 22 |
| Overall Study | Withdrawal by Subject | 4 | 0 | 0 |
Baseline characteristics
| Characteristic | Target Cmax 420 µg/mL | Target Cmax 360 μg/mL | Albumin-Tailored Dose | Total |
|---|---|---|---|---|
| Age, Continuous | 56.88 years STANDARD_DEVIATION 11.12 | 59.88 years STANDARD_DEVIATION 8.98 | 56.83 years STANDARD_DEVIATION 10.37 | 57.39 years STANDARD_DEVIATION 10.51 |
| Race/Ethnicity, Customized African Decent (black) | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 50 Participants | 18 Participants | 31 Participants | 99 Participants |
| Race/Ethnicity, Customized East Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Italy | 9 Participants | 8 Participants | 11 Participants | 28 Participants |
| Region of Enrollment Russia | 12 Participants | 0 Participants | 0 Participants | 12 Participants |
| Region of Enrollment United States | 32 Participants | 10 Participants | 21 Participants | 63 Participants |
| Sex: Female, Male Female | 53 Participants | 18 Participants | 32 Participants | 103 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 47 / 53 | 18 / 18 | 30 / 32 |
| serious Total, serious adverse events | 21 / 53 | 5 / 18 | 15 / 32 |
Outcome results
Primary
Percentage of Participants With Complete Response and Partial Response (Objective Response Rate)
Objective 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. 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: Baseline to measured progressive disease up to 12.68 months
Population: All participants who received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Target Cmax 420 µg/mL | Percentage of Participants With Complete Response and Partial Response (Objective Response Rate) | 7.5 percentage of participants |
| Target Cmax 360 μg/mL | Percentage of Participants With Complete Response and Partial Response (Objective Response Rate) | 0 percentage of participants |
| Albumin-Tailored Dose | Percentage of Participants With Complete Response and Partial Response (Objective Response Rate) | 3.1 percentage of participants |
Secondary
Duration of Response
The duration of response (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 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.
Time frame: Time of response to time of measured progressive disease up to 12.68 months
Population: All participants who received at least one dose of the study drug and had complete response (CR) or partial response (PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Target Cmax 420 µg/mL | Duration of Response | 5.03 months |
| Albumin-Tailored Dose | Duration of Response | 12.68 months |
Secondary
Duration of Stable Disease
Duration of stable disease is defined from date of documented stable disease (SD) or better to first date of progressive disease or death from any cause (assessed every cycle during study therapy, or every 2 months during post-therapy until disease progression or death). 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 or death due to any cause up to 21.26 months
Population: All participants who received at least one dose of the study drug and stable disease or better.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Target Cmax 420 µg/mL | Duration of Stable Disease | 3.71 months |
| Target Cmax 360 μg/mL | Duration of Stable Disease | 3.27 months |
| Albumin-Tailored Dose | Duration of Stable Disease | 3.78 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 including the 30-day follow-up period. 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 43.91 months
Population: All participants who received at least one dose of the study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Target Cmax 420 µg/mL | Number of Participants With Adverse Events (Safety) | Serious Adverse Events | 21 Participants |
| Target Cmax 420 µg/mL | Number of Participants With Adverse Events (Safety) | Other Nonserious Adverse Events | 47 Participants |
| Target Cmax 360 μg/mL | Number of Participants With Adverse Events (Safety) | Serious Adverse Events | 5 Participants |
| Target Cmax 360 μg/mL | Number of Participants With Adverse Events (Safety) | Other Nonserious Adverse Events | 18 Participants |
| Albumin-Tailored Dose | Number of Participants With Adverse Events (Safety) | Serious Adverse Events | 15 Participants |
| Albumin-Tailored Dose | Number of Participants With Adverse Events (Safety) | Other Nonserious Adverse Events | 30 Participants |
Secondary
Overall Survival
Overall survival is defined as the time from date of first treatment to the date of death due to any cause. For participants who were alive, overall survival was censored at their last contact.
Time frame: First treatment to death due to any cause up to 42.91 months
Population: All participants who received at least one dose of the study drug. The numbers of participants censored are 11 (Target Cmax 420 µg/mL group), 6 (Target Cmax 360 µg/mL group) and 14 (Albumin-Tailored Dose group).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Target Cmax 420 µg/mL | Overall Survival | 13.08 months |
| Target Cmax 360 μg/mL | Overall Survival | 10.09 months |
| Albumin-Tailored Dose | Overall Survival | 11.63 months |
Secondary
Percentage of Participants With Complete Response, Partial Response, and Stable Disease (Clinical Benefit Rate)
Clinical Benefit Rate is complete response (CR) + partial response (PR) + stable disease (SD) as classified by the investigator 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. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Clinical benefit rate is calculated as a total number of participants with CR or PR or SD divided by the total number of participants treated multiplied by 100.
Time frame: Baseline to measured progressive disease up to 21.26 months
Population: All participants who received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Target Cmax 420 µg/mL | Percentage of Participants With Complete Response, Partial Response, and Stable Disease (Clinical Benefit Rate) | 45.3 percentage of participants |
| Target Cmax 360 μg/mL | Percentage of Participants With Complete Response, Partial Response, and Stable Disease (Clinical Benefit Rate) | 61.1 percentage of participants |
| Albumin-Tailored Dose | Percentage of Participants With Complete Response, Partial Response, and Stable Disease (Clinical Benefit Rate) | 34.4 percentage of participants |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of LY573636
Time frame: Predose up to 2 hours postdose in Cycles 1 and 2
Population: All participants who received at least one dose of the study drug and had pharmacokinetics data at the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Target Cmax 420 µg/mL | Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 | Cycle 1 | 368.4 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 8.9 |
| Target Cmax 420 µg/mL | Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 | Cycle 2 | 323.0 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 13.6 |
| Target Cmax 360 μg/mL | Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 | Cycle 1 | 324.1 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 7.9 |
| Target Cmax 360 μg/mL | Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 | Cycle 2 | 326.1 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 14.5 |
| Albumin-Tailored Dose | Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 | Cycle 1 | 340.9 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 15.4 |
| Albumin-Tailored Dose | Pharmacokinetics: Maximum Concentration (Cmax) of LY573636 | Cycle 2 | 320.7 micrograms/milliliter (µg/mL) | Geometric Coefficient of Variation 17.7 |
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 Response Evaluation Criteria In Solid Tumors (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 due to any cause up to 21.26 months
Population: All participants who received at least 1 dose of the study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Target Cmax 420 µg/mL | Progression Free Survival | 1.87 months |
| Target Cmax 360 μg/mL | Progression Free Survival | 2.40 months |
| Albumin-Tailored Dose | Progression Free Survival | 2.10 months |
Other Pre-specified
Number of Participants Who Died Due to Progressive Disease During the 30 Days Following Discontinuation From Study Treatment
Time frame: Study treatment discontinuation up to 30 days post study treatment discontinuation
Population: All participants who received at least one dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Target Cmax 420 µg/mL | Number of Participants Who Died Due to Progressive Disease During the 30 Days Following Discontinuation From Study Treatment | 2 Participants |
| Target Cmax 360 μg/mL | Number of Participants Who Died Due to Progressive Disease During the 30 Days Following Discontinuation From Study Treatment | 3 Participants |
| Albumin-Tailored Dose | Number of Participants Who Died Due to Progressive Disease During the 30 Days Following Discontinuation From Study Treatment | 1 Participants |