Clinical trial NCT00709995: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Renal Cell Carcinoma
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2008-07-03
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression Free Survival (PFS) in Part 2
timeFrame: Randomization to Measured Progressive Disease (PD) (Up to 24 Months)
Secondary outcomes:
measure: Overall Survival (OS) in Part 2
timeFrame: Randomization to Death from Any Cause (Up to 24 Months)
measure: Time-To-Tumor Progression in Part 2
timeFrame: Randomization to the Date of Objective Progressive Disease or Date of Death due to Study Disease, whichever came first (Up to 24 Months)
measure: Number of Participants With Adverse Events (AEs) or Serious AEs (SAEs) in Part 1
timeFrame: Randomization to Study Completion (Up to 6 Cycles)
measure: 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
timeFrame: Cycle 1 Day 15: Predose, 2, 4, and 6 - 8 hours, Up to 12 Hours Post dose
measure: PK: Maximum Concentration at Steady State (Cmax,ss) of Enzastaurin + LSN326020 + Total Analytes in Part 1
timeFrame: Cycle 1 Day 15: Predose, 2, 4, and 6 - 8 hours, Up to 12 Hours Post dose
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: 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
country: France
facility: 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
country: Italy
facility: 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
country: Poland
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) Mon - Fri 9AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: