Back to resultsA Study for Participants With Metastatic Renal Cell Carcinoma
Primary Purpose
Metastatic Renal Cell Carcinoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Enzastaurin
Sunitinib
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Renal Cell Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Participants with metastatic Renal Cell Carcinoma (RCC) who have not received prior treatment with systemic (adjuvant or neoadjuvant) therapy for RCC (including targeted therapy such as tyrosine kinase inhibitors or bevacizumab, immunotherapy, chemotherapy, hormonal, or investigational therapy)
- Histologically confirmed RCC with metastases with a component of clear (conventional) cell histology
- Evidence of unidimensional measurable disease, measured by computed tomography (CT) scan or magnetic resonance imaging (MRI)
- Primary tumor has been surgically removed by nephrectomy or nephron-sparing surgery
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- Participants must sign an informed consent document
Exclusion Criteria:
- Have received prior treatment with sunitinib or enzastaurin
- Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry
Have had any of the following within 12 months prior to study drug administration:
- myocardial infarction,
- severe/unstable angina,
- coronary/peripheral artery bypass graft,
- symptomatic congestive heart failure (CHF),
- cerebrovascular accident,
- transient ischemic attack, or
- pulmonary embolism
- Note: Ongoing treatment with therapeutic doses of Coumadin® (warfarin) or a derivative of Coumadin or phenprocoumon is not allowed, but prophylactic, low-dose Coumadin (≤ 2 mg daily) for deep vein thrombosis is allowed. In such cases, prothrombin time/international normalization ratio (PT/INR) should be very closely monitored as clinically indicated
- Ongoing cardiac arrhythmias >New York Health Association Class II, atrial fibrillation of any grade, or prolongation of the QTc interval to >450 millisecond (msec) for males or >470 msec for females.
- Have uncontrolled hypertension [>150/100 millimeter of mercury (mm/Hg) despite optimal medical therapy], or history of poor compliance with antihypertensive treatment
- Require concomitant use of potent Cytochrome P450 3A4 (CYP3A4) inducer, for example, rifampicin or potent CYP3A inhibitors, such as ketoconazole.
- Significant surgery or radiation therapy <4 weeks of starting study treatment. Prior palliative radiotherapy to metastatic lesion(s) is/are permitted, provided there is at least 1 measurable lesion that has not been irradiated
- Participants who are pregnant or breast feeding
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.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Part 1 Arm A: Enzastaurin + Sunitinib
Part 2 Arm B: Sunitinib + Placebo
Arm Description
(Cohort 1): On cycle 1, day 1 a loading dose 125 milligram (mg) of Enzastaurin was administered by mouth orally, (BID) twice a day, followed by Enzastaurin 125 mg administered, twice a day, Days 2 through 42 of a 6-week cycle. (Cohort 2): Cycle 1, Day 1 loading dose 375 mg of Enzastaurin administered po three times a day (TID), followed by 250 mg, po, BID continuously until disease progression, unacceptable toxicity, death, or discontinuation from the study for any other reason. Sunitinib 50 mg was administered orally, once daily, Days 1-28, then rest (no drug given) days 29-42. Phase 2 (Part 2): Randomized Double-Blind: Dosing was determined by Part 1. Part 2 was not activated per recommendation of safety review committee. Enzastaurin: Cycle 1, Day 1 loading dose 375 mg administered orally, (TID) three times a day, followed by Part 1 dose twice a day on Days 2-42 of 6 week cycle. Sunitinib: 50 mg administered orally, once daily, on Days 1-28, then rest Days 29-42.
Part 2 was not activated per recommendation of safety review committee. Sunitinib: 50 mg administered orally, once daily, Day 1-28, then rest Days 29-42. Placebo: Cycle 1 Day 1 loading dose 3 tablets on Day 1, then 2 tablets daily, days 2-42.
Outcomes
Primary Outcome Measures
Progression Free Survival (PFS) in Part 2
Progression-free survival (PFS) was defined as the number of months between the date of randomization and the date of first documented disease progression or the date of death due to any cause, whichever came first.
Secondary Outcome Measures
Overall Survival (OS) in Part 2
OS time was defined as the number of months between the date of randomization and the date of death due to any cause.
Time-To-Tumor Progression in Part 2
Time to tumor progression (TTP) at initial treatment was defined as the number of months between date of randomization and the date of first documented disease progression or the date of death due to disease under study, whichever came first.
Number of Participants With Adverse Events (AEs) or Serious AEs (SAEs) in Part 1
Clinically significant events were defined as serious adverse events, regardless of causality. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.
Pharmacokinetics (PK): Area Under Concentration Time Curve During One Dosing Interval at Steady State (AUCτ,ss) of Enzastaurin + Metabolite (LSN326020) + Total Analytes in Part 1
Pharmacokinetics (PK) was assessed in participants to determine the area under the concentration time curve during one dosing interval at steady state (AUCτ,ss) of Enzastaurin, LSN326020 and total Analytes. τ equals 12 hours for Enzastaurin, LSN326020 and total Analytes.
PK: Maximum Concentration at Steady State (Cmax,ss) of Enzastaurin + LSN326020 + Total Analytes in Part 1
PK was assessed in participants to determine the maximum concentration at steady state (Cmax, ss) of Enzastaurin + LSN326020 + total analytes.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00709995
Brief Title
A Study for Participants With Metastatic Renal Cell Carcinoma
Official Title
Dose Finding and Randomized, Multicenter, Placebo-Controlled, Phase 2 Study of Enzastaurin and Sunitinib Versus Placebo and Sunitinib in Patients With Metastatic Renal Cell Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
June 30, 2008 (Actual)
Primary Completion Date
February 15, 2010 (Actual)
Study Completion Date
September 5, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will compare the effects of Enzastaurin plus Sunitinib versus Sunitinib alone in metastatic Renal Cell Cancer.
Detailed Description
This is a multicenter, Phase 2 study of enzastaurin and sunitinib versus placebo and sunitinib as first-line therapy in participants with metastatic renal cell carcinoma, containing 2 parts. Part 1 is a safety lead-in study with 12 participants and possible dose escalation. Part 2 is a randomized, double-blind, Phase 2 study in 110 participants.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Renal Cell Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
17 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1 Arm A: Enzastaurin + Sunitinib
Arm Type
Experimental
Arm Description
(Cohort 1): On cycle 1, day 1 a loading dose 125 milligram (mg) of Enzastaurin was administered by mouth orally, (BID) twice a day, followed by Enzastaurin 125 mg administered, twice a day, Days 2 through 42 of a 6-week cycle.
(Cohort 2): Cycle 1, Day 1 loading dose 375 mg of Enzastaurin administered po three times a day (TID), followed by 250 mg, po, BID continuously until disease progression, unacceptable toxicity, death, or discontinuation from the study for any other reason.
Sunitinib 50 mg was administered orally, once daily, Days 1-28, then rest (no drug given) days 29-42.
Phase 2 (Part 2): Randomized Double-Blind: Dosing was determined by Part 1. Part 2 was not activated per recommendation of safety review committee.
Enzastaurin: Cycle 1, Day 1 loading dose 375 mg administered orally, (TID) three times a day, followed by Part 1 dose twice a day on Days 2-42 of 6 week cycle.
Sunitinib: 50 mg administered orally, once daily, on Days 1-28, then rest Days 29-42.
Arm Title
Part 2 Arm B: Sunitinib + Placebo
Arm Type
Placebo Comparator
Arm Description
Part 2 was not activated per recommendation of safety review committee.
Sunitinib: 50 mg administered orally, once daily, Day 1-28, then rest Days 29-42.
Placebo: Cycle 1 Day 1 loading dose 3 tablets on Day 1, then 2 tablets daily, days 2-42.
Intervention Type
Drug
Intervention Name(s)
Enzastaurin
Other Intervention Name(s)
LY317615
Intervention Description
Administered orally
Intervention Type
Drug
Intervention Name(s)
Sunitinib
Intervention Description
Administered orally
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered orally
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS) in Part 2
Description
Progression-free survival (PFS) was defined as the number of months between the date of randomization and the date of first documented disease progression or the date of death due to any cause, whichever came first.
Time Frame
Randomization to Measured Progressive Disease (PD) (Up to 24 Months)
Secondary Outcome Measure Information:
Title
Overall Survival (OS) in Part 2
Description
OS time was defined as the number of months between the date of randomization and the date of death due to any cause.
Time Frame
Randomization to Death from Any Cause (Up to 24 Months)
Title
Time-To-Tumor Progression in Part 2
Description
Time to tumor progression (TTP) at initial treatment was defined as the number of months between date of randomization and the date of first documented disease progression or the date of death due to disease under study, whichever came first.
Time Frame
Randomization to the Date of Objective Progressive Disease or Date of Death due to Study Disease, whichever came first (Up to 24 Months)
Title
Number of Participants With Adverse Events (AEs) or Serious AEs (SAEs) in Part 1
Description
Clinically significant events were defined as serious adverse events, regardless of causality. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.
Time Frame
Randomization to Study Completion (Up to 6 Cycles)
Title
Pharmacokinetics (PK): Area Under Concentration Time Curve During One Dosing Interval at Steady State (AUCτ,ss) of Enzastaurin + Metabolite (LSN326020) + Total Analytes in Part 1
Description
Pharmacokinetics (PK) was assessed in participants to determine the area under the concentration time curve during one dosing interval at steady state (AUCτ,ss) of Enzastaurin, LSN326020 and total Analytes. τ equals 12 hours for Enzastaurin, LSN326020 and total Analytes.
Time Frame
Cycle 1 Day 15: Predose, 2, 4, and 6 - 8 hours, Up to 12 Hours Post dose
Title
PK: Maximum Concentration at Steady State (Cmax,ss) of Enzastaurin + LSN326020 + Total Analytes in Part 1
Description
PK was assessed in participants to determine the maximum concentration at steady state (Cmax, ss) of Enzastaurin + LSN326020 + total analytes.
Time Frame
Cycle 1 Day 15: Predose, 2, 4, and 6 - 8 hours, Up to 12 Hours Post dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants with metastatic Renal Cell Carcinoma (RCC) who have not received prior treatment with systemic (adjuvant or neoadjuvant) therapy for RCC (including targeted therapy such as tyrosine kinase inhibitors or bevacizumab, immunotherapy, chemotherapy, hormonal, or investigational therapy)
Histologically confirmed RCC with metastases with a component of clear (conventional) cell histology
Evidence of unidimensional measurable disease, measured by computed tomography (CT) scan or magnetic resonance imaging (MRI)
Primary tumor has been surgically removed by nephrectomy or nephron-sparing surgery
Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
Participants must sign an informed consent document
Exclusion Criteria:
Have received prior treatment with sunitinib or enzastaurin
Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry
Have had any of the following within 12 months prior to study drug administration:
myocardial infarction,
severe/unstable angina,
coronary/peripheral artery bypass graft,
symptomatic congestive heart failure (CHF),
cerebrovascular accident,
transient ischemic attack, or
pulmonary embolism
Note: Ongoing treatment with therapeutic doses of Coumadin® (warfarin) or a derivative of Coumadin or phenprocoumon is not allowed, but prophylactic, low-dose Coumadin (≤ 2 mg daily) for deep vein thrombosis is allowed. In such cases, prothrombin time/international normalization ratio (PT/INR) should be very closely monitored as clinically indicated
Ongoing cardiac arrhythmias >New York Health Association Class II, atrial fibrillation of any grade, or prolongation of the QTc interval to >450 millisecond (msec) for males or >470 msec for females.
Have uncontrolled hypertension [>150/100 millimeter of mercury (mm/Hg) despite optimal medical therapy], or history of poor compliance with antihypertensive treatment
Require concomitant use of potent Cytochrome P450 3A4 (CYP3A4) inducer, for example, rifampicin or potent CYP3A inhibitors, such as ketoconazole.
Significant surgery or radiation therapy <4 weeks of starting study treatment. Prior palliative radiotherapy to metastatic lesion(s) is/are permitted, provided there is at least 1 measurable lesion that has not been irradiated
Participants who are pregnant or breast feeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) Mon - Fri 9AM - 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
Vienna
ZIP/Postal Code
A1090
Country
Austria
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
Villejuif
ZIP/Postal Code
94805
Country
France
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
Rome
ZIP/Postal Code
00149
Country
Italy
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
Warsaw
ZIP/Postal Code
00909
Country
Poland
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
IPD Sharing Time Frame
Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
IPD Sharing Access Criteria
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
IPD Sharing URL
https://www.clinicalstudydatarequest.com/
Learn more about this trial
A Study for Participants With Metastatic Renal Cell Carcinoma
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