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

A Randomized Phase 2 Study of LY2181308 in Combination With Docetaxel Versus Docetaxel in Hormone Refractory Prostate Cancer

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: docetaxel; Drug: Prednisone; Drug: LY2181308 sodium

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Augsburg, Germany, 86150
    • 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.
  • Frankfurt, Germany, 60488
    • 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.
  • Hannover, Germany, 30625
    • 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.
  • Heidelberg, Germany, 69115
    • 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.
  • Heilbronn, Germany, D-74078
    • 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.
  • Homburg, Germany, 66421
    • 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.
  • Muenchen-Planegg, Germany, 82152
    • 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.
• Poland
  • Gdansk, Poland, 80-219
    • 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.
  • Kielce, Poland, 25-734
    • 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.
  • Olsztyn, Poland, 10-228
    • 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.
  • Warsaw, Poland, 02-781
    • 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.
• Spain
  • Barcelona, Spain, 08036
    • 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.
  • Benidorm, Spain, 03501
    • 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.
  • Elda, Spain, 03600
    • 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.
  • Madrid, Spain, 28050
    • 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.
  • Pamplona, Spain, 31008
    • 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.
• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38138
      • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A: Docetaxel; Standard of care (SOC) docetaxel 75 mg/m² intravenously every 3 weeks and prednisone 5 mg orally twice daily continuously while receiving docetaxel therapy	Drug: docetaxel; 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.; Drug: Prednisone; Prednisone 5 mg given orally twice daily continuously while receiving docetaxel therapy
Experimental: B: LY2181308 + Docetaxel; LY2181308 administered with docetaxel 75 mg/m² intravenously every 3 weeks and prednisone 5 mg orally twice daily continuously while receiving docetaxel	Drug: docetaxel; 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.; Drug: Prednisone; Prednisone 5 mg given orally twice daily continuously while receiving docetaxel therapy; Drug: LY2181308 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to measured progressive disease or death due to any cause up to 44.68 months
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.	First treatment dose up to 19 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	First treatment dose 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
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.	Baseline, 18 months
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.	First treatment to death due to any cause up to 45.54 months
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 of response to time of measured progressive disease up to 41.00 months
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.	Baseline to measured progressive disease up to 41.00 months
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.	Baseline, 21 days
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.	3 months
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.	3 months

Other Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9AM-5PM Eastern time (UTC/GMT-5 hours, EST), Eli Lilly and Company

Publications and helpful links

General Publications

• de Liano AG, Reig O, Mellado B, Martin C, Rull EU, Maroto JP. Prognostic and predictive value of plasma testosterone levels in patients receiving first-line chemotherapy for metastatic castrate-resistant prostate cancer. Br J Cancer. 2014 Apr 29;110(9):2201-8. doi: 10.1038/bjc.2014.189. Epub 2014 Apr 10.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: February 28, 2008
• First Submitted That Met QC Criteria: March 19, 2008
• First Posted (Estimate): March 24, 2008

Study Record Updates

• Last Update Posted (Actual): April 3, 2019
• Last Update Submitted That Met QC Criteria: March 11, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Hormone Refractory Prostate Cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Docetaxel; Prednisone
• Other Study ID Numbers: 10461; H8Z-MC-JACR (Other Identifier: Eli Lilly and Company)