A Phase 2 Study With Enzastaurin Plus Chemotherapy or Placebo Plus Chemotherapy for Prostate Cancer Patients
- Conditions
- Prostate Cancer
- Interventions
- Registration Number
- NCT00466440
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The purpose of the study is to compare the response rates for prostate cancer patients taking chemotherapy plus enzastaurin versus chemotherapy plus placebo.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 108
- You are at least 18 years old.
- You live close enough to the doctor's office to attend all of your required visits.
- You have not been treated with chemotherapy for your prostate cancer.
- Your organs must be functioning properly.
- You are unable to swallow pills.
- You have another serious illness besides your prostate cancer.
- You have taken another experimental drug within the last 30 days.
- You have a serious heart condition.
- You are receiving another anti-cancer therapy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description docetaxel + prednisone + placebo placebo Regimen B: docetaxel 75 mg/m\^2, IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po, BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by po, QD placebo for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding. docetaxel + prednisone + enzastaurin enzastaurin Regimen A: docetaxel 75 milligrams per square meter (mg/m\^2), intravenous (IV) is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 milligrams (mg) oral (po), twice daily (BID) every day. In Cycle 1, enzastaurin is given as a loading dose of 1125 mg on the day prior to docetaxel and prednisone therapy, followed by enzastaurin 500 mg po, daily (QD) for the remaining Period 2 (chemotherapy) and Period 3 (maintenance). docetaxel + prednisone + enzastaurin docetaxel Regimen A: docetaxel 75 milligrams per square meter (mg/m\^2), intravenous (IV) is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 milligrams (mg) oral (po), twice daily (BID) every day. In Cycle 1, enzastaurin is given as a loading dose of 1125 mg on the day prior to docetaxel and prednisone therapy, followed by enzastaurin 500 mg po, daily (QD) for the remaining Period 2 (chemotherapy) and Period 3 (maintenance). docetaxel + prednisone + enzastaurin prednisone Regimen A: docetaxel 75 milligrams per square meter (mg/m\^2), intravenous (IV) is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 milligrams (mg) oral (po), twice daily (BID) every day. In Cycle 1, enzastaurin is given as a loading dose of 1125 mg on the day prior to docetaxel and prednisone therapy, followed by enzastaurin 500 mg po, daily (QD) for the remaining Period 2 (chemotherapy) and Period 3 (maintenance). docetaxel + prednisone + enzastaurin (modified Regimen A) enzastaurin Modified Regimen A, including pharmacokinetic (PK) characterization: Participants were treated with a modified investigational regimen with no dose escalation: docetaxel 75 mg/m2, IV was administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po, BID every day. In Cycle 1, enzastaurin was given as a loading dose of 1125 mg starting on Day 4, followed by enzastaurin 500 mg po, QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance). docetaxel + prednisone + enzastaurin (modified Regimen A) prednisone Modified Regimen A, including pharmacokinetic (PK) characterization: Participants were treated with a modified investigational regimen with no dose escalation: docetaxel 75 mg/m2, IV was administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po, BID every day. In Cycle 1, enzastaurin was given as a loading dose of 1125 mg starting on Day 4, followed by enzastaurin 500 mg po, QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance). docetaxel + prednisone + enzastaurin (modified Regimen A) docetaxel Modified Regimen A, including pharmacokinetic (PK) characterization: Participants were treated with a modified investigational regimen with no dose escalation: docetaxel 75 mg/m2, IV was administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po, BID every day. In Cycle 1, enzastaurin was given as a loading dose of 1125 mg starting on Day 4, followed by enzastaurin 500 mg po, QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance).
- Primary Outcome Measures
Name Time Method Part 2: Percentage of Participants With Objective Tumor Response (Response Rate) Baseline up to 3 years Response using Response Evaluation Criteria In Solid Tumors (RECIST). Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=small changes that do not meet above criteria. Objective response rate (%)=number of objective responders divided by the number of participants qualified for efficacy analysis \*100, where objective responders are those participants who have met criteria either for CR or PR.
- Secondary Outcome Measures
Name Time Method Prostate-Specific Androgen (PSA) Velocity at 2 Months Baseline up to 2 months PSA is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is considered the most effective test currently available for the early detection of prostate cancer. PSA velocity is computed for each participant by means of linear regression on the logarithm of PSA. The linear regression fits a line through the logarithm of the PSA value on the y-axis, and the time from baseline on the x-axis with the baseline PSA value at time zero. The resulting slope is PSA velocity.
Prostate-Specific Androgen (PSA) Velocity at 3 Months Baseline up to 3 months PSA is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is considered the most effective test currently available for the early detection of prostate cancer. PSA velocity is computed for each participant by means of linear regression on the logarithm of PSA. The linear regression fits a line through the logarithm of the PSA value on the y-axis, and the time from baseline on the x-axis with the baseline PSA value at time zero. The resulting slope is PSA velocity.
Part 2: Duration of Response First objective response to PD/death/PSA returning to 50% or more than the original baseline value (up to 616 days) Duration of response is defined as the time from date of objective response to progressive disease (PD) or death or prostate-specific androgen (PSA) returning to at least 50% from original baseline value.
Percentage of Participants Exhibiting a Decline in Prostate-Specific Androgen (PSA) From Baseline ≥30% Within First 3 Months of Treatment Baseline up to 3 months PSA is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is considered the most effective test currently available for the early detection of prostate cancer. Decline in PSA of ≥30% from baseline within the first 3 months of treatment was calculated.
Tumor Markers Baseline up to 36 months Pharmacogenomic (PGx) work on S032 was cancelled due to the limited number of tissue samples collected and the lack of clinical efficacy (responders) to enzastaurin. Potential biomarkers would have been assessed by dividing participants into low and high expression classes.
Part I: Pharmacokinetic (PK) Parameter: Maximum Observed Drug Concentration During a Dosing Interval at Steady State (Cmax,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020) Part 1: Cycle 1, Day 21 - predose 2, 4, 6, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 2, 3, 4, 8, and 24 hours postdose Cmax,ss was calculated using concentration versus time data of enzastaurin, LSN326020, and total analyte (enzastaurin + LSN326020). Data are reported as Geometric Mean and Geometric Coefficient of Variation (%).
Pharmacokinetic (PK) Parameter: Area Under the Concentration Versus Time Curve During 1 Dosing Interval at Steady State (AUCτ,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020) Part 1: Cycle 1, Day 21 - predose 2, 4, 6, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 2, 3, 4, 8, and 24 hours postdose; Part 2: Cycle 2, Day 1 - predose, 1-3, and 4-9 hours postdose AUCτ,ss was calculated using concentration versus time data of enzastaurin, LSN326020, and total analyte (enzastaurin + LSN326020). Data are reported as Geometric Mean and Geometric Coefficient of Variation (%).
Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Docetaxel Part 1: Cycle 1, Day 1 - predose 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose Cmax was calculated using concentration versus time data of docetaxel. Data are reported as Geometric Mean and Geometric Coefficient of Variation (%).
Part 2: Overall Survival (OS) Baseline to death (up to 642 days) Overall survival (OS) time is defined as the time from the date of diagnosis to the date of death from any cause. For participants who are still alive at the time of analysis, survival time will be censored at the last contact date.
Part 2: Progression Free Survival (PFS) Baseline to measured PD (up to 487 days) PFS was defined as the time from the date of study enrollment to the first date of objectively determined progressive disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST version 1.0). PD is ≥20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. For participants not known to have died and who did not have PD, PFS was censored at the date of the last progression-free assessment. For participants who received subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to disease progression or death, PFS was censored at the date of last progression-free assessment prior to the initiation of post-discontinuation systemic anticancer therapy. No participant completed a full cycle of therapy and thus no formal analysis was performed.
Number of Participants With Adverse Events (AEs) Baseline through 3 years A listing of serious AEs (SAEs) and all other non-serious AEs is included in the Reported Adverse Event Module.
Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-∞]) of Docetaxel Part 1: Cycle 1, Day 1 - predose 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose AUC(0-∞) was calculated using concentration versus time data of docetaxel. Data are reported as Geometric Mean and Geometric Coefficient of Variation (%).
Trial Locations
- Locations (1)
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
🇮🇹San Sisto, Italy