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Phase 2 Trial of Enzastaurin in Prostate Cancer in Participants Who Have Had Hormonal and Chemotherapy

Primary Purpose

Prostate Cancer

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

enzastaurin

About this trial

This is an interventional treatment trial for Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

You are expected to be alive in the 12 weeks.
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 (cohort 1).
Must have evidence of androgen-independent PSA-progressive disease without a history of or current (as judged by the investigator) clinical or radiographic evidence of metastatic disease with castrate levels of testosterone (<50 ng/dL) maintained by luteinizing hormone-releasing hormone (LHRH) agonist or bilateral orchiectomy following standard anti-androgen withdrawal. NOTE: PSA progression is defined as have rising PSA values of <=5 ng/mL (at least 3 measurements 1 week apart) with castrate levels of testosterone <50 ng/dL following appropriate antiandrogen withdrawal, without evidence of metastases. (cohort 1)
No prior systemic chemotherapy for prostate cancer. No prior chemotherapy for any other indication within 2 years of study entry. NOTE: Participants previously treated with chemotherapy in the adjuvant/neoadjuvant setting were not be eligible. (cohort 1)
You have had one prior docetaxel-based chemotherapy regimen (cohort 2).
You have evidence of metastatic prostate cancer with bone or soft tissue disease (cohort 2).
Must have evidence of docetaxel-resistant, androgen-independent metastatic prostate cancer with bone or soft tissue disease (PSA only participants are not eligible) defined as either: clinical, PSA or radiographic disease progression while receiving docetaxel-based therapy or PSA and/or radiographic progression at any time after completion of a docetaxel-containing regimen with PSA progression defined as a 25% increase in PSA from the post docetaxel value or interval progression in known metastatic sites of disease or development of new sites of disease on bone scan or computed tomography (CT) imaging. Note: Participants who discontinued a docetaxel-containing regimen due to toxicity or any other reasons not related to disease progression while on treatment, and were not able to complete at least 2 cycles, were not be eligible. (cohort 2)
Your organs must be functioning properly.

Exclusion Criteria:

You are unable to swallow pills.
You have another 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.

Sites / Locations

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Enzastaurin-Cohort 1

Enzastaurin-Cohort 2

Arm Description

Chemo-naive participants who had androgen-independent prostate cancer with rising prostate-specific antigen (PSA) levels but no clinical or radiographic evidence of metastatic disease. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.

Participants with progressed, metastatic prostate cancer who had received prior treatment with a docetaxel-containing agent. Participants were given 1125 mg loading dose of enzastaurin on Day 1 of Cycle 1 (28-day cycle) only, and thereafter 500 mg enzastaurin once daily.

Outcomes

Primary Outcome Measures

Cohort 1 - Number of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate)

Objective responders were defined as participants (pts) in Cohort 1 who met prostate-specific antigen (PSA) response criteria. PSA Complete response (CR) was defined as a decrease in PSA to an undetectable level (<0.2 ng/mL) confirmed by a second value obtained at least 4 weeks apart and without clinical or radiographic evidence of disease. PSA Partial Response (PR) was defined as a decrease in PSA of >=50% at any time during the study. The decline of >=50% in PSA must be from a baseline value of >5 ng/mL and must be confirmed by a second value obtained at least 4 weeks apart and without clinical or radiographic evidence of disease.

Cohort 2 - Progression-free Survival (PFS)-Overall

PFS was defined as the time from date of enrollment to first occurrence of (1) tumor progression (defined per Response Evaluation Criteria In Solid Tumors [RECIST]) for soft tissue lesions, and/or appearance of >=2 new lesions on bone scan (confirmed >=6 weeks later); (2) skeletal event (pathological bone fracture and/or need for palliative radiotherapy); (3) symptomatic progression (worsening of Eastern Cooperative Oncology Group (ECOG) performance status (PS) and/or weight loss >10% from baseline and/or increase in analgesic consumption and pain); or (4) Death due to any cause. PFS was censored at date of last objective progression-free observation for participants who were still alive and had not progressed. Participants who took any subsequent systemic anticancer therapy prior to progression or death were censored at date of last objective progression-free disease assessment prior to the date of the subsequent systemic anticancer therapy.

Secondary Outcome Measures

Cohort 1 - Number of Participants With a 3-month PSA Level Decline of Greater Than or Equal to 30%

Number of participants exhibiting a PSA level decline from baseline of greater than or equal to 30% within the first 3 months of study.

Cohort 1 - PSA Velocity

PSA velocity is defined as the rate of change in the PSA level during the first 2 and 3 months of the study.

Cohort 1 - Progression-free Survival (PFS)-Overall

Progression free survival (PFS) is defined as the time from the date of enrollment to the first occurrence of PSA progression or objective progression defined as development of radiographic evidence of metastatic disease irrespective of PSA value or death due to any cause. PSA progression is defined as (a) for participants in whom a 50% decline in PSA has not been achieved, this is defined as 25% increase over baseline or nadir whichever is lower and an increase in the absolute value of PSA level by 5 ng/mL that is confirmed by another value of PSA confirmed at least 4 weeks apart; (b) for participants in whom a 50% decline in PSA has been achieved, this is defined as 50% increase over the nadir and an increase in the absolute value of PSA level by 5 ng/mL that is confirmed by another PSA level at least 4 weeks apart.

Cohort 1 - Duration of Response

Duration of response was the date of first objective assessment of CR or PR to the date of first progression or death due to any cause. Progression of disease defined as:1) PSA progression: (a) in whom a 50% decline in PSA has not been achieved, defined as 25% increase over baseline or nadir whichever is lower and an increase in the absolute value of PSA level by 5 ng/mL and confirmed by another PSA at least 4 weeks apart, (b) in whom a 50% decline in PSA has been achieved, defined as 50% increase over the nadir and an increase in the absolute value of PSA level by 5 ng/mL and confirmed by another PSA level at least 4 weeks apart. 2) Objective Progression defined as radiographic evidence of metastatic disease irrespective of PSA value or 3) death due to any cause. Duration of response was censored on the date of discontinuation or last assessment for those participants who were alive without progression.

Cohort 2 - 3-month PSA Level Decline of Greater Than or Equal to 30%

Number of participants exhibiting a PSA level decline from baseline of greater than or equal to 30% within the first 3 months of study.

Cohort 2 - PSA Velocity

PSA velocity is defined as the rate of change in the PSA level during the first 2 and 3 months of the study.

Cohort 2 - Number of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate)

Objective responders in Cohort 2 met either CR or PR for composite criteria of PSA and RECIST. CR was defined as a decrease in PSA to an undetectable level (<0.2 ng/mL) confirmed by a second value at least 4 weeks apart and without clinical or radiographic evidence of disease per RECIST and normalization of bone scan. Bone only disease CR is normalization of bone scan with achievement of a nondetectable PSA confirmed 4-weeks after initial undetectable PSA. PR was defined as a decrease from baseline by 50% in PSA at any time during the study and confirmed by a second value at least 4 weeks apart and having at least a 30% decrease in sum of longest diameter of target lesions per RECIST and stable or improved bone scan.

Cohort 2 - Percentage of Participants With Progression Free Survival (PFS) at 6 Months and 12 Months

Percentage of participants who did not meet the following criteria at 6 months and at 12 months: disease progression defined per RECIST for soft tissue lesions and/or the appearance of 2 or more new lesions on bone scan, or skeletal event (any pathological bone fracture, and/or need for palliative radiotherapy), or symptomatic progression (worsening ECOG performance status) and/or weight loss >10% from baseline and/or increase in analgesic consumption and pain, or death due to any cause. PFS was censored at the date of the most recent assessment for those who were still alive at the time of analysis and did not have evidence of tumor progression. Participants who took any subsequent systemic anticancer therapy prior to progression or death, PFS was censored at the date of the last objective progression-free disease assessment prior to the date of the subsequent systemic anticancer therapy. Percent=(number of participants meeting PFS criteria/number of randomized)x100.

Cohort 2 - Overall Survival

Overall survival is the duration from enrollment to death. For participants who were alive, overall survival was censored at the last contact.

Cohort 2 - Duration of Response

Duration of response was the date of first objective assessment of CR or PR to the date of first progression or death due to any cause. Progression of disease defined as:1) PSA progression: (a) in whom a 50% decline in PSA has not been achieved, defined as 25% increase over baseline or nadir whichever is lower and an increase in the absolute value of PSA level by 5 ng/mL and confirmed by another PSA at least 4 weeks apart, (b) in whom a 50% decline in PSA has been achieved, defined as 50% increase over the nadir and an increase in the absolute value of PSA level by 5 ng/mL and confirmed by another PSA level at least 4 weeks apart. 2) Objective Progression defined as radiographic evidence of metastatic disease irrespective of PSA value. 3) death due to any cause. Duration of response was censored on the date of discontinuation or last assessment for those participants who were alive without progression.

Full Information

NCT ID

NCT00428714

First Posted

January 26, 2007

Last Updated

November 4, 2020

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT00428714

Brief Title

Phase 2 Trial of Enzastaurin in Prostate Cancer in Participants Who Have Had Hormonal and Chemotherapy

Official Title

Phase 2 Trial Oral Enzastaurin in Prostate Cancer Patients Who Have Rising PSA (1) During Hormonal Manipulation and (2) After First-Line Cytotoxic Chemotherapy

Study Type

Interventional

2. Study Status

Record Verification Date

November 2020

Overall Recruitment Status

Completed

Study Start Date

January 2007 (undefined)

Primary Completion Date

June 2009 (Actual)

Study Completion Date

January 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose is to see how quickly two different types of prostate cancer participants respond when taking enzastaurin. Cohort 1 - asymptomatic participants with androgen-independent prostate-specific antigen (PSA)-progressive disease without clinical or radiographic evidence of metastatic disease. Cohort 2 - participants with androgen-independent metastatic prostate cancer (documented bone or soft tissue metastases) with rising PSA, clinical, radiographic disease progression following one prior docetaxel-based regimen

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

73 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Enzastaurin-Cohort 1

Arm Type

Experimental

Arm Description

Arm Title

Enzastaurin-Cohort 2

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

enzastaurin

Other Intervention Name(s)

LY317615

Intervention Description

Administered orally

Primary Outcome Measure Information:

Title

Cohort 1 - Number of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate)

Description

Time Frame

Baseline to Measured Progressive Disease, Death, Unacceptable Toxicities, or Study Closure Whichever Occurred First (up to 56 weeks)

Title

Cohort 2 - Progression-free Survival (PFS)-Overall

Description

Time Frame

baseline to first occurrence of tumor progression, skeletal event, symptomatic progression, or death (up to 31.3 weeks)

Secondary Outcome Measure Information:

Title

Cohort 1 - Number of Participants With a 3-month PSA Level Decline of Greater Than or Equal to 30%

Description

Number of participants exhibiting a PSA level decline from baseline of greater than or equal to 30% within the first 3 months of study.

Time Frame

baseline to 3 months

Title

Cohort 1 - PSA Velocity

Description

PSA velocity is defined as the rate of change in the PSA level during the first 2 and 3 months of the study.

Time Frame

baseline, 2 months and 3 months

Title

Cohort 1 - Progression-free Survival (PFS)-Overall

Description

Time Frame

baseline to date of disease progression, death, unacceptable toxicities, or study closure whichever occurred first (up to 56 weeks)

Title

Cohort 1 - Duration of Response

Description

Time Frame

time of response to progressive disease, death, unacceptable toxicities, or study closure whichever occurred first (up to 56 weeks)

Title

Cohort 2 - 3-month PSA Level Decline of Greater Than or Equal to 30%

Description

Number of participants exhibiting a PSA level decline from baseline of greater than or equal to 30% within the first 3 months of study.

Time Frame

baseline to 3 months

Title

Cohort 2 - PSA Velocity

Description

PSA velocity is defined as the rate of change in the PSA level during the first 2 and 3 months of the study.

Time Frame

baseline, 2 months and 3 months

Title

Cohort 2 - Number of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate)

Description

Time Frame

baseline to first occurrence of tumor progression, skeletal event, symptomatic progression, or death (up to 31.3 months)

Title

Cohort 2 - Percentage of Participants With Progression Free Survival (PFS) at 6 Months and 12 Months

Description

Time Frame

6 months and 12 months

Title

Cohort 2 - Overall Survival

Description

Overall survival is the duration from enrollment to death. For participants who were alive, overall survival was censored at the last contact.

Time Frame

baseline to date of death from any cause (up to 69.6 weeks)

Title

Cohort 2 - Duration of Response

Description

Duration of response was the date of first objective assessment of CR or PR to the date of first progression or death due to any cause. Progression of disease defined as:1) PSA progression: (a) in whom a 50% decline in PSA has not been achieved, defined as 25% increase over baseline or nadir whichever is lower and an increase in the absolute value of PSA level by 5 ng/mL and confirmed by another PSA at least 4 weeks apart, (b) in whom a 50% decline in PSA has been achieved, defined as 50% increase over the nadir and an increase in the absolute value of PSA level by 5 ng/mL and confirmed by another PSA level at least 4 weeks apart. 2) Objective Progression defined as radiographic evidence of metastatic disease irrespective of PSA value. 3) death due to any cause. Duration of response was censored on the date of discontinuation or last assessment for those participants who were alive without progression.

Time Frame

time of response to first occurrence of tumor progression, skeletal event, symptomatic progression, or death (up to 31.3 months)

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: You are expected to be alive in the 12 weeks. 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 (cohort 1). Must have evidence of androgen-independent PSA-progressive disease without a history of or current (as judged by the investigator) clinical or radiographic evidence of metastatic disease with castrate levels of testosterone (<50 ng/dL) maintained by luteinizing hormone-releasing hormone (LHRH) agonist or bilateral orchiectomy following standard anti-androgen withdrawal. NOTE: PSA progression is defined as have rising PSA values of <=5 ng/mL (at least 3 measurements 1 week apart) with castrate levels of testosterone <50 ng/dL following appropriate antiandrogen withdrawal, without evidence of metastases. (cohort 1) No prior systemic chemotherapy for prostate cancer. No prior chemotherapy for any other indication within 2 years of study entry. NOTE: Participants previously treated with chemotherapy in the adjuvant/neoadjuvant setting were not be eligible. (cohort 1) You have had one prior docetaxel-based chemotherapy regimen (cohort 2). You have evidence of metastatic prostate cancer with bone or soft tissue disease (cohort 2). Must have evidence of docetaxel-resistant, androgen-independent metastatic prostate cancer with bone or soft tissue disease (PSA only participants are not eligible) defined as either: clinical, PSA or radiographic disease progression while receiving docetaxel-based therapy or PSA and/or radiographic progression at any time after completion of a docetaxel-containing regimen with PSA progression defined as a 25% increase in PSA from the post docetaxel value or interval progression in known metastatic sites of disease or development of new sites of disease on bone scan or computed tomography (CT) imaging. Note: Participants who discontinued a docetaxel-containing regimen due to toxicity or any other reasons not related to disease progression while on treatment, and were not able to complete at least 2 cycles, were not be eligible. (cohort 2) Your organs must be functioning properly. Exclusion Criteria: You are unable to swallow pills. You have another 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

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.

City

Los Angeles

State/Province

California

ZIP/Postal Code

90025

Country

United States

Facility Name

City

Stanford

State/Province

California

ZIP/Postal Code

94305

Country

United States

Facility Name

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06520

Country

United States

Facility Name

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

Facility Name

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89135

Country

United States

Facility Name

City

Buffalo

State/Province

New York

ZIP/Postal Code

14263

Country

United States

Facility Name

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

Facility Name

City

Lancaster

State/Province

Pennsylvania

ZIP/Postal Code

17605

Country

United States

Facility Name

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38120

Country

United States

Facility Name

City

Madison

State/Province

Wisconsin

ZIP/Postal Code

53792

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

20369375

Citation

Dreicer R, Garcia J, Hussain M, Rini B, Vogelzang N, Srinivas S, Somer B, Zhao YD, Kania M, Raghavan D. Oral enzastaurin in prostate cancer: a two-cohort phase II trial in patients with PSA progression in the non-metastatic castrate state and following docetaxel-based chemotherapy for castrate metastatic disease. Invest New Drugs. 2011 Dec;29(6):1441-8. doi: 10.1007/s10637-010-9428-0. Epub 2010 Apr 6.

Results Reference

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Phase 2 Trial of Enzastaurin in Prostate Cancer in Participants Who Have Had Hormonal and Chemotherapy

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