AMG 386, 20060159 Phase 2, RCC 1st Line in Combination With Sorafenib

Study Overview
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Brief Summary
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This is a phase 2, randomized, double-blind, placebo controlled, multi-center study to estimate the improvement in progression free survival (PFS) and evaluate the safety and tolerability of AMG 386 in combination with sorafenib in the treatment of subjects with advanced clear cell carcinoma of the kidney.

Official Title
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A Randomized, Double Blinded, Multi-Center Phase 2 Study to Estimate the Efficacy and Evaluate the Safety and Tolerability of Sorafenib in Combination With AMG 386 or Placebo In Subjects With Metastatic Clear Cell Carcinoma of the Kidney

Conditions
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Advanced Renal Cell Carcinoma

Intervention / Treatment
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* Drug: AMG 386
* Drug: Sorafenib
* Drug: AMG 386 placebo IV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have a histologically confirmed metastatic RCC with a clear cell component Low or intermediate risk according to the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk classification. Measurable disease with at least one unidimensionally measurable lesion per RECIST guidelines with modifications Adequate organ and hematological function as evidenced by laboratory studies conducted at Screening. ECOG of 0 or 1 Exclusion Criteria: Disease Related Known history of central nervous system metastases. Previous treatment (excluding surgery and palliative radiotherapy) for advanced or metastatic renal cell carcinoma Focal radiation therapy for palliation of pain from bony metastases within 14 days of randomization. Medications Currently or previously treated with inhibitors of VEGF. Currently or previously treated with inhibitors of angiopoietin or Tie2. Currently or previously treated with bevacizumab. General Medical Diagnosis of acute pancreatitis. Myocardial infarction, cerebrovascular accident, transient ischemic attack, percutaneous transluminal coronary angioplasty/stent, congestive heart failure, grade 2 or greater peripheral vascular disease, arrhythmias not controlled by outpatient medication, or unstable angina within 1 year prior to randomization Major surgery within 30 days before randomization or still recovering from prior surgery Uncontrolled hypertension as defined as diastolic > 90 mmHg OR systolic >150 mmHg. Anti-hypertensive medications are permitted. Other Other investigational procedures are excluded Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br> | Drug: AMG 386<br>* 3 mg/kg or 10mg/kg IV weekly until unacceptable toxicity or disease progression<br>Drug: Sorafenib<br>* 400 mg PO BID<br>Drug: AMG 386 placebo IV<br>* AMG 386 placebo IV<br>|
| Experimental: Arm B<br> | Drug: AMG 386<br>* 3 mg/kg or 10mg/kg IV weekly until unacceptable toxicity or disease progression<br>Drug: Sorafenib<br>* 400 mg PO BID<br>|
| Active Comparator: Arm C<br> | Drug: Sorafenib<br>* 400 mg PO BID<br>Drug: AMG 386 placebo IV<br>* AMG 386 placebo IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival |  | 2 3/4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) |  | 2 3/4 years | 
| Duration of response (DOR) |  | 2 3/4 years | 
| Change in continuous measures of tumor burden |  | 2 3/4 years | 
| Time-adjusted area under the curve (AUC) for the FACT-Kidney Cancer Symptom Index (FKSI-15) scale score from baseline through disease progression with imputation for missing data |  | 2 3/4 years | 
| Incidence of AEs and significant laboratory changes |  | 2 3/4 years | 
| Incidence of the occurrence of anti-AMG 386 antibody formation |  | 2 3/4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic clear cell carcinoma of the kidney, RCC