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A Study of an Experimental Chemotherapy Combination to Treat Hormone Refractory Prostate Cancer

Phase 2
Completed
Conditions
Prostate Cancer
Interventions
Registration Number
NCT00642018
Lead Sponsor
Eli Lilly and Company
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
154
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
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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
B: LY2181308 + DocetaxelLY2181308 sodiumLY2181308 administered with docetaxel 75 mg/m² intravenously every 3 weeks and prednisone 5 mg orally twice daily continuously while receiving docetaxel
A: DocetaxelPrednisoneStandard of care (SOC) docetaxel 75 mg/m² intravenously every 3 weeks and prednisone 5 mg orally twice daily continuously while receiving docetaxel therapy
A: DocetaxeldocetaxelStandard of care (SOC) docetaxel 75 mg/m² intravenously every 3 weeks and prednisone 5 mg orally twice daily continuously while receiving docetaxel therapy
B: LY2181308 + DocetaxeldocetaxelLY2181308 administered with docetaxel 75 mg/m² intravenously every 3 weeks and prednisone 5 mg orally twice daily continuously while receiving docetaxel
B: LY2181308 + DocetaxelPrednisoneLY2181308 administered with docetaxel 75 mg/m² intravenously every 3 weeks and prednisone 5 mg orally twice daily continuously while receiving docetaxel
Primary Outcome Measures
NameTimeMethod
Progression-free Survival (PFS) in Participants With Hormone Refractory Prostate Cancer (HRPC) Administered LY2181308 Sodium Plus Docetaxel Compared to Docetaxel AloneBaseline 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.

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.

Secondary Outcome Measures
NameTimeMethod
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.

Adverse Event ProfileFirst 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.

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
Estimate Overall SurvivalFirst 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 ResponseTime 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.

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.

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.

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.

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Pamplona, Spain

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