Prostate Cancer
Conditions
Keywords
Hormone Refractory Prostate Cancer
Brief summary
The primary purpose of this study is to determine whether LY2181308 in combination with docetaxel is safe and effective treatment for hormone refractory prostate cancer patients.
Interventions
DRUGdocetaxel
Docetaxel 75 milligrams per square meter (mg/m²) intravenously on Day 1 of a 21-day cycle. Patients may receive up to 10 cycles of study therapy or until progressive disease. Additional cycles may be approved by sponsor as long as the patient is benefitting from therapy.
DRUGLY2181308 sodium
LY2181308 sodium (referred to as LY2181308 throughout this record) administered weekly plus docetaxel 75 mg/m² intravenously administered every 21 days. Patients may receive up to 10 cycles of study therapy or until progressive disease. Additional cycles may be approved by sponsor as long as the patient is benefitting from therapy.
DRUGPrednisone
Prednisone 5 mg given orally twice daily continuously while receiving docetaxel therapy
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed adenocarcinoma of the prostate which is metastatic and/or unresectable * Hormone refractory prostate cancer defined as progressive based by documented 2 increase Prostate specific antigen (PSA) values over a previous reference value. * Eastern Cooperative Oncology Group (ECOG) status 0-2 * Adequate hematological functions, liver and renal functions
Exclusion criteria
* Known hypersensitivity to docetaxel or taxane therapy * Documented central nervous system or leptomeningeal metastasis at time of study entry * Had prior treatment with chemotherapy, bone-seeking radionuclides in past 6 weeks prior to enrollment, or radiotherapy involving more than 25% of marrow producing area. * Evidence of painful and/or destructive bone metastases for which radiation therapy, bisphosphonates or bone-seeking radionuclides are necessary. * Have received treatment in the last 30 day with a drug which has not received regulatory approval for any indication at the time of study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (Safety) | First treatment dose up to 19 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. The participants received maximum 24 cycles of treatment (1cycle = 3 weeks). Safety data were collected up to 24 cycles plus 30 days of follow-up for a total up to 19 months. |
| Progression-free Survival (PFS) in Participants With Hormone Refractory Prostate Cancer (HRPC) Administered LY2181308 Sodium Plus Docetaxel Compared to Docetaxel Alone | Baseline to measured progressive disease or death due to any cause up to 44.68 months | PFS is 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. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. For participants who had no PD or death, PFS was censored at their last contact. Participants were still followed for PFS after they stopped receiving study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of Docetaxel: Area Under the Concentration Time Curve From Time Zero to Infinity (AUC0-infinity) | Predose up to 8 hours postdose in Cycle 1 | — |
| Prostate Specific Antigen (PSA) Kinetics: Percentage of Participants With PSA Response (Response Rate) | Baseline, 18 months | PSA response was defined as a post-baseline PSA level decline of at least 50% relative to the baseline value. Response rate calculated as 100\*n/N where n=the number of participants with responses and N=the total number of participants treated. |
| Estimate Overall Survival | First treatment to death due to any cause up to 45.54 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. Participants were still followed for overall survival after they stopped receiving study drug. |
| Estimate Duration of Overall Response | Time of response to time of measured progressive disease up to 41.00 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 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. For participants who had no progression or death, the duration of response was censored at their last contact. |
| Change From Baseline to Day 21 in Granulocyte Colony Stimulating Factor(G-CSF) (Assess Biomarker Responses) | Baseline, 21 days | G-CSF \[international units per milliliter (IU/mL)\] was used to estimate biomarker responses and is presented as the percentage change from baseline. |
| Functional Assessment of Cancer Therapy-Prostate Cancer (FACT-P) Total Score at 3 Months (Participant Reported Outcomes) | 3 months | The FACT-P is a 39-item participant-rated questionnaire which assesses physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and additional prostate cancer specific concerns (12 items). All items are scored from 0 (not at all) to 4 (very much). The total FACT-P score ranges from 0-156, with higher scores representing a better quality of life with fewer symptoms. |
| Functional Assessment of Cancer Therapy-General (FACT-G) Total Score at 3 Months (Evaluate Clinical Symptoms) | 3 months | The total FACT-G is the sum of 4 subscale scores on the FACT-Prostate Cancer (FACT-P) participant-rated questionnaire representing general cancer symptoms: physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), and functional well-being (7 items). All items are scored from 0 (not at all) to 4 (very much). The total FACT-G score ranges from 0-108, with higher scores representing a better quality of life with fewer symptoms. |
| Percentage of Participants With Complete Response or Partial Response (Overall Response Rate) | Baseline to measured progressive disease up to 41.00 months | Overall response rate was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) per the Response Evaluation Criteria In Solid Tumors (RECIST) criteria. 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. |
| Adverse Event Profile | First treatment dose up to 19 months | Data presented are the number of participants with all treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), discontinuations due to SAEs and AEs, and deaths that occurred in this study that were assessed by investigators as possibly related to study drug. The participants received maximum 24 cycles of treatment (1cycle = 3 weeks). Safety data were collected up to 24 cycles plus 30 days of follow-up for a total up to 19 months. |
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
Germany, Poland, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel Docetaxel 75 milligrams per square meter (mg/m²) intravenously on Day 1 of a 21-day cycle. Prednisone 5 mg given orally twice daily continuously while receiving docetaxel therapy. | 51 |
| LY2181308 + Docetaxel LY2181308 loading dose of 750 mg intravenously on Days 1-3, followed by a maintenance dose of 750 mg on Days 8 and 15 during first 21-day cycle. LY2181308 750 mg intravenously on Days 1, 8 and 15 in combination with docetaxel 75 mg/m² on Day 1 of every 21-day cycle from Cycle 2 and beyond. Prednisone 5 mg given orally twice daily continuously while receiving docetaxel therapy. | 98 |
| Total | 149 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 36 |
| Overall Study | Death | 0 | 3 |
| Overall Study | Entry Criteria Not Met | 0 | 1 |
| Overall Study | Physician Decision | 0 | 10 |
| Overall Study | Progressive Disease | 13 | 18 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 10 |
Baseline characteristics
| Characteristic | LY2181308 + Docetaxel | Total | Docetaxel |
|---|---|---|---|
| Age, Continuous | 68.25 years STANDARD_DEVIATION 8.7 | 68.20 years STANDARD_DEVIATION 8.89 | 68.09 years STANDARD_DEVIATION 9.33 |
| Race/Ethnicity, Customized African | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 94 Participants | 143 Participants | 49 Participants |
| Race/Ethnicity, Customized East Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Germany | 33 Participants | 47 Participants | 14 Participants |
| Region of Enrollment Poland | 29 Participants | 46 Participants | 17 Participants |
| Region of Enrollment Puerto Rico | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Spain | 25 Participants | 41 Participants | 16 Participants |
| Region of Enrollment United States | 10 Participants | 14 Participants | 4 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 98 Participants | 149 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 50 / 51 | 94 / 98 |
| serious Total, serious adverse events | 11 / 51 | 47 / 98 |
Outcome results
Primary
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. The participants received maximum 24 cycles of treatment (1cycle = 3 weeks). Safety data were collected up to 24 cycles plus 30 days of follow-up for a total up to 19 months.
Time frame: First treatment dose up to 19 months
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Docetaxel | Number of Participants With Adverse Events (Safety) | Serious Adverse Events | 11 Participants |
| Docetaxel | Number of Participants With Adverse Events (Safety) | Other Nonserious Adverse Events | 50 Participants |
| LY2181308 + Docetaxel | Number of Participants With Adverse Events (Safety) | Serious Adverse Events | 47 Participants |
| LY2181308 + Docetaxel | Number of Participants With Adverse Events (Safety) | Other Nonserious Adverse Events | 94 Participants |
Primary
Progression-free Survival (PFS) in Participants With Hormone Refractory Prostate Cancer (HRPC) Administered LY2181308 Sodium Plus Docetaxel Compared to Docetaxel Alone
PFS is 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. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. For participants who had no PD or death, PFS was censored at their last contact. Participants were still followed for PFS after they stopped receiving study drug.
Time frame: Baseline to measured progressive disease or death due to any cause up to 44.68 months
Population: All randomized participants who received at least one dose of the study drug. The numbers of participants censored were 10 (Docetaxel group) and 22 (LY2181308 + Docetaxel group).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel | Progression-free Survival (PFS) in Participants With Hormone Refractory Prostate Cancer (HRPC) Administered LY2181308 Sodium Plus Docetaxel Compared to Docetaxel Alone | 9.00 months |
| LY2181308 + Docetaxel | Progression-free Survival (PFS) in Participants With Hormone Refractory Prostate Cancer (HRPC) Administered LY2181308 Sodium Plus Docetaxel Compared to Docetaxel Alone | 8.64 months |
Secondary
Adverse Event Profile
Data presented are the number of participants with all treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), discontinuations due to SAEs and AEs, and deaths that occurred in this study that were assessed by investigators as possibly related to study drug. The participants received maximum 24 cycles of treatment (1cycle = 3 weeks). Safety data were collected up to 24 cycles plus 30 days of follow-up for a total up to 19 months.
Time frame: First treatment dose up to 19 months
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Docetaxel | Adverse Event Profile | SAEs | 5 Participants |
| Docetaxel | Adverse Event Profile | Discontinuations due to SAEs | 1 Participants |
| Docetaxel | Adverse Event Profile | Discontinuations due to AEs | 6 Participants |
| Docetaxel | Adverse Event Profile | Death | 0 Participants |
| Docetaxel | Adverse Event Profile | TEAEs | 45 Participants |
| LY2181308 + Docetaxel | Adverse Event Profile | Death | 0 Participants |
| LY2181308 + Docetaxel | Adverse Event Profile | TEAEs | 91 Participants |
| LY2181308 + Docetaxel | Adverse Event Profile | SAEs | 27 Participants |
| LY2181308 + Docetaxel | Adverse Event Profile | Discontinuations due to AEs | 22 Participants |
| LY2181308 + Docetaxel | Adverse Event Profile | Discontinuations due to SAEs | 3 Participants |
Secondary
Change From Baseline to Day 21 in Granulocyte Colony Stimulating Factor(G-CSF) (Assess Biomarker Responses)
G-CSF \[international units per milliliter (IU/mL)\] was used to estimate biomarker responses and is presented as the percentage change from baseline.
Time frame: Baseline, 21 days
Population: All randomized participants who received at least one dose of study drug and had G-CSF measurement at baseline and 21 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel | Change From Baseline to Day 21 in Granulocyte Colony Stimulating Factor(G-CSF) (Assess Biomarker Responses) | -32.5 percentage change |
| LY2181308 + Docetaxel | Change From Baseline to Day 21 in Granulocyte Colony Stimulating Factor(G-CSF) (Assess Biomarker Responses) | 233.3 percentage change |
Secondary
Estimate Duration of Overall 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 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. For participants who had no progression or death, the duration of response was censored at their last contact.
Time frame: Time of response to time of measured progressive disease up to 41.00 months
Population: All randomized participants who received at least one dose of the study drug and had complete response (CR) or partial response (PR). The numbers of participants censored were 3 (Docetaxel group) and 1 (LY2181308 + Docetaxel group).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel | Estimate Duration of Overall Response | 10.81 months |
| LY2181308 + Docetaxel | Estimate Duration of Overall Response | 9.66 months |
Secondary
Estimate 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. Participants were still followed for overall survival after they stopped receiving study drug.
Time frame: First treatment to death due to any cause up to 45.54 months
Population: All randomized participants who received at least one dose of study drug. The numbers of participants censored were 25 (Docetaxel group) and 49 (LY2181308 + Docetaxel group).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel | Estimate Overall Survival | 29.04 months |
| LY2181308 + Docetaxel | Estimate Overall Survival | 27.04 months |
Secondary
Functional Assessment of Cancer Therapy-General (FACT-G) Total Score at 3 Months (Evaluate Clinical Symptoms)
The total FACT-G is the sum of 4 subscale scores on the FACT-Prostate Cancer (FACT-P) participant-rated questionnaire representing general cancer symptoms: physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), and functional well-being (7 items). All items are scored from 0 (not at all) to 4 (very much). The total FACT-G score ranges from 0-108, with higher scores representing a better quality of life with fewer symptoms.
Time frame: 3 months
Population: All randomized participants who received at least one dose of study drug and had FACT-G assessment at 3 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel | Functional Assessment of Cancer Therapy-General (FACT-G) Total Score at 3 Months (Evaluate Clinical Symptoms) | 84 units on a scale |
| LY2181308 + Docetaxel | Functional Assessment of Cancer Therapy-General (FACT-G) Total Score at 3 Months (Evaluate Clinical Symptoms) | 80 units on a scale |
Secondary
Functional Assessment of Cancer Therapy-Prostate Cancer (FACT-P) Total Score at 3 Months (Participant Reported Outcomes)
The FACT-P is a 39-item participant-rated questionnaire which assesses physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and additional prostate cancer specific concerns (12 items). All items are scored from 0 (not at all) to 4 (very much). The total FACT-P score ranges from 0-156, with higher scores representing a better quality of life with fewer symptoms.
Time frame: 3 months
Population: All randomized participants who received at least one dose of study drug and had FACT-P assessment at 3 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel | Functional Assessment of Cancer Therapy-Prostate Cancer (FACT-P) Total Score at 3 Months (Participant Reported Outcomes) | 117 units on a scale |
| LY2181308 + Docetaxel | Functional Assessment of Cancer Therapy-Prostate Cancer (FACT-P) Total Score at 3 Months (Participant Reported Outcomes) | 115 units on a scale |
Secondary
Percentage of Participants With Complete Response or Partial Response (Overall Response Rate)
Overall response rate was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) per the Response Evaluation Criteria In Solid Tumors (RECIST) criteria. 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 41.00 months
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel | Percentage of Participants With Complete Response or Partial Response (Overall Response Rate) | 21.6 percentage of participants |
| LY2181308 + Docetaxel | Percentage of Participants With Complete Response or Partial Response (Overall Response Rate) | 10.2 percentage of participants |
Secondary
Pharmacokinetics of Docetaxel: Area Under the Concentration Time Curve From Time Zero to Infinity (AUC0-infinity)
Time frame: Predose up to 8 hours postdose in Cycle 1
Population: All randomized participants who received at least one dose of the study drug and had pharmacokinetics data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Docetaxel | Pharmacokinetics of Docetaxel: Area Under the Concentration Time Curve From Time Zero to Infinity (AUC0-infinity) | 825 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 56.6 |
| LY2181308 + Docetaxel | Pharmacokinetics of Docetaxel: Area Under the Concentration Time Curve From Time Zero to Infinity (AUC0-infinity) | 799 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 59.7 |
Secondary
Prostate Specific Antigen (PSA) Kinetics: Percentage of Participants With PSA Response (Response Rate)
PSA response was defined as a post-baseline PSA level decline of at least 50% relative to the baseline value. Response rate calculated as 100\*n/N where n=the number of participants with responses and N=the total number of participants treated.
Time frame: Baseline, 18 months
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel | Prostate Specific Antigen (PSA) Kinetics: Percentage of Participants With PSA Response (Response Rate) | 56.9 percentage of participants |
| LY2181308 + Docetaxel | Prostate Specific Antigen (PSA) Kinetics: Percentage of Participants With PSA Response (Response Rate) | 56.1 percentage of participants |
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 randomized participants who received at least one dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Docetaxel | Number of Participants Who Died Due to Progressive Disease During the 30 Days Following Discontinuation From Study Treatment | 1 Participants |
| LY2181308 + Docetaxel | Number of Participants Who Died Due to Progressive Disease During the 30 Days Following Discontinuation From Study Treatment | 0 Participants |