A Study for Participants With Metastatic Renal Cell Carcinoma

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

This study will compare the effects of Enzastaurin plus Sunitinib versus Sunitinib alone in metastatic Renal Cell Cancer.

Study Overview

• Status: Completed
• Conditions: Metastatic Renal Cell Carcinoma
• Intervention / Treatment: Drug: Placebo; Drug: Enzastaurin; Drug: Sunitinib

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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, A1090
    • 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.
• France
  • Villejuif, France, 94805
    • 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.
• Italy
  • Rome, Italy, 00149
    • 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
  • Warsaw, Poland, 00909
    • 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 and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Arm A: Enzastaurin + Sunitinib; (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.	Drug: Enzastaurin; Administered orally; Other Names: LY317615; Drug: Sunitinib; Administered orally
Placebo Comparator: Part 2 Arm B: Sunitinib + Placebo; 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.	Drug: Placebo; Administered orally; Drug: Sunitinib; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Randomization to Measured Progressive Disease (PD) (Up to 24 Months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Randomization to Death from Any Cause (Up to 24 Months)
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.	Randomization to the Date of Objective Progressive Disease or Date of Death due to Study Disease, whichever came first (Up to 24 Months)
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.	Randomization to Study Completion (Up to 6 Cycles)
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.	Cycle 1 Day 15: Predose, 2, 4, and 6 - 8 hours, Up to 12 Hours Post dose
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.	Cycle 1 Day 15: Predose, 2, 4, and 6 - 8 hours, Up to 12 Hours Post dose

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Lilly Clinical Trial Registry

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2008
• Primary Completion (Actual): February 15, 2010
• Study Completion (Actual): September 5, 2018

Study Registration Dates

• First Submitted: June 30, 2008
• First Submitted That Met QC Criteria: July 2, 2008
• First Posted (Estimate): July 3, 2008

Study Record Updates

• Last Update Posted (Actual): September 30, 2019
• Last Update Submitted That Met QC Criteria: September 3, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: 11531; H6Q-MC-S061 (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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 Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)