Renal cell carcinoma
Conditions
Sponsors
Eli Lilly and company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] Patients with metastatic 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) [2] Histologically confirmed RCC with metastases with a component of clear (conventional) cell histology [3] Evidence of unidimensionally measurable disease (=1 malignant tumor mass that can be accurately measured in at least 1 dimension =20 mm with conventional computed tomography (CT) or magnetic resonance imaging (MRI) scan, or =10 mm with spiral CT scan. (If spiral CT scan is used, minimum lesion size should be twice the reconstruction interval used. For example, if reconstruction size is 7 mm, lesion size should be =14 mm). CT/MRI should be performed within 4 weeks prior to study entry Note: Bone lesions, ascites, peritoneal carcinomatosis or miliary lesions, pleural or pericardial effusions, lymphangitis of the skin or lung, cystic lesions, or irradiated lesions are not considered measurable. [4] Primary tumor has been surgically removed by nephrectomy or nephron-sparing surgery [5] ECOG performance status score of 0 or 1 (see Protocol Attachment S061.5) [6] Have adequate bone marrow, liver, and renal function, as assessed by the following laboratory requirements, to be conducted within 7 days prior to treatment: (ULN/LLN = upper/lower limit of normal) ? Hemoglobin >9.0 g/dL ? Absolute neutrophil count (ANC) =1.5 x 103 µL ? Platelet count =100 x 103/µL ? Total bilirubin =1.5 x ULN ? Serum calcium within 10% of normal range? ? Serum creatinine =2 x ULN ? Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3 x ULN (or =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: [13] Have received prior treatment with sunitinib or enzastaurin [14] 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 [15] 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, PT/INR should be very closely monitored as clinically indicated. [16] Ongoing cardiac arrhythmias >New York Health Association Class II (Protocol Attachment S061.6), atrial fibrillation of any grade, or prolongation of the QTc interval to >450 msec for males or >470 msec for females [17] Have uncontrolled hypertension (>150/100 mm/Hg despite optimal medical therapy), or history of poor compliance with antihypertensive treatment [18] Have active, clinically serious bacterial or fungal infection more than NCI CTCAE Grade 2 [19] Have known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B/C [20] Have history of or known brain metastases, spinal cord compression, carcinomatous meningitis, or evidence of brain or leptomeningeal disease on screening CT or MRI scan [21] Have history of documented central nervous system disease unrelated to cancer; for example, uncontrolled seizures, unless adequately treated with standard medical therapy [22] Have evidence of bleeding diathesis, NCI CTCAE Grade 3 hemorrhage 325 mg/day) [31] Have serious nonhealing wounds, acute or nonhealing ulcers, or bone fractures [32] Are unable or unwilling to discontinue use of carbamazepine, phenobarbital, or phenytoin at least 14 days prior to study therapy [33] Are unable to swallow tablets.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this Phase 2 study is to compare the progression-free survival in enzastaurin and sunitinib therapy versus sunitinib and placebo in the first-line setting for patients with metastatic clear-cell RCC;Secondary Objective: The secondary objectives of the study are: • to compare the following time-to-event efficacy variables between treatment arms: - time to tumor progression (TTP) - overall survival (OS) - to estimate duration of overall response in each treatment arm • to compare the objective response rate (complete response [CR] + partial response [PR]) between treatment arms • to compare the rate of clinical benefit (CR + PR + stable disease [SD]) between treatment arms • to assess the safety and adverse events in both treatment arms • to characterize the pharmacokinetics (PK) of enzastaurin and sunitinib when administered in combination • to assess biomarkers (for example, PKCß, GSK3ß, S6K, PTEN, CREB) relevant to enzastaurin and disease state, and their correlation to clinical outcome. ;Primary end point(s): The primary endpoint for Part 1 (Safety lead in) is to evaluate the safety of the combination of enzastaurin plus sunitinib. The primary endpoint for Part 2 is to compare progression-free survival (PFS) between the two arms of treatment. | — |
Countries
Austria, France, Italy, Poland, Spain
Outcome results
None listed