Overview

This trial is active, not recruiting.

Condition metastatic renal cell carcinoma
Treatments enzastaurin, sunitinib, placebo
Phase phase 2
Targets VEGF, FLT-3, KIT, PDGF
Sponsor Eli Lilly and Company
Start date June 2008
End date February 2010
Trial size 122 participants
Trial identifier NCT00709995, 11531, H6Q-MC-S061

Summary

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
Arm
(Experimental)
Part 1: Dose escalation. Enzastaurin (Cohort 1): Cycle 1, Day 1 loading dose 250 milligram (mg) administered by mouth (po), twice a day (BID), followed by 125 mg, po, BID on Days 2-42 of 6 week cycle. Enzastaurin (Cohort 2) Cycle 1, Day 1 loading dose 375 mg 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 (Cohort 1 and 2): 50 mg administered po, every day (QD), on Days 1-28, then rest (no drug given) on Days 29-42. Part 2: Randomized Double-Blind: Dosing for Part 2 will be determined by outcome of Part 1. Phase 2 was not activated per recommendation of safety review committee. Enzastaurin: Cycle 1, Day 1 loading dose 375 mg administered po, TID, followed by Phase 1 dose BID on Days 2-42 of 6 week cycle. Sunitinib: 50 mg administered po, QD, on Days 1-28, then rest Days 29-42.
enzastaurin LY317615
Administered orally
sunitinib
Administered orally
(Placebo Comparator)
Arm B is in Part 2 of the study only. Sunitinib: 50 mg administered po, QD Day 1-28, then rest Days 29-42. Placebo: Cycle 1 Day 1 loading dose 3 tablets on Day 1, then 2 tablets QD on Days 2-42.
sunitinib
Administered orally
placebo
Administered orally

Primary Outcomes

Measure
Part 2: Progression Free Survival
time frame: Randomization to Measured Progressive Disease (PD) (Estimated up to 24 Months)

Secondary Outcomes

Measure
Part 2: Overall Survival
time frame: Randomization to Death from Any Cause (Estimated up to 24 Months)
Time-To-Tumor Progression
time frame: Randomization to the Date of Objective PD (Estimated up to 24 Months)
Number of Participants with Adverse Events (AEs) or Serious AEs
time frame: Baseline to Study Completion (Estimated up to 5 Years)
Part 1: Pharmacokinetics (PK): Area Under Concentration Time Curve during One Dosing Interval at Steady State (AUCτ,ss) of Enzastaurin, LSN326020, Total Analytes and Sunitinib
time frame: Cycle 1 Day 15 Predose up to 12 Hours Post dose

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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
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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Eli Lilly and Company.