A Phase II Uncontrolled Study of BAY73-4506 in Previously Untreated Patients With Metastatic or Unresectable RCC

Study Overview
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Brief Summary
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This is a uncontrolled, open-label, non-randomized Phase II study of oral BAY73-4506 to evaluate the response rate of BAY73-4506 in previously untreated patients with metastatic or unresectable renal cell cancer (RCC).

Detailed Description
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The final analysis of efficacy will be performed after last patient has been treated for at least 6 months. Additional periodic safety and efficacy data reviews will be performed for any patients continuing to receive study drug afterwards.

Official Title
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A Phase II Uncontrolled Study of BAY73-4506 in Previously Untreated Patients With Metastatic or Unresectable Renal Cell Cancer (RCC)

Conditions
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Carcinoma, Renal Cell

Intervention / Treatment
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* Drug: Regorafenib (Stivarga, BAY73-4506)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients >/= 18 years of age. Patients, who suffer from unresectable and/or metastatic, measurable predominantly clear cell RCC (renal cell carcinoma histologically) or cytologically documented. Patients must be previously untreated for advanced disease. Prior palliative radiation therapy is allowed if the target lesion(s) are not included within the radiation field and no more than 30% of the bone marrow is irradiated. Patients who have at least one uni-dimensional measurable lesion by computed tomography (CT-scan) or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST). Patients with Intermediate or Low risk per the Motzer score. Patients who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1. Adequate bone marrow, renal and hepatic function as assessed by the following laboratory requirements to be conducted within 7 days prior to study drug treatment Exclusion Criteria: Patients who have received prior systemic treatment regimens for RCC. Uncontrolled/unstable cardiac disease Uncontrolled hypertension Active clinically serious infections (> Common Terminology Criteria for Adverse Events [CTCAE] grade 2 ) History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C. Known history or symptomatic metastatic brain or meningeal tumours Patients with seizure disorder requiring medication Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event >/= CTCAE Grade 3 within 4 weeks of first dose of study. Pregnant or breast-feeding patients

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regorafenib (Stivarga, BAY73-4506)<br>Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle | Drug: Regorafenib (Stivarga, BAY73-4506)<br>* Patients will be treated with BAY73-4506 160 mg po qd for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off). Patients will continue treatment with BAY73-4506 until disease progression, intolerable toxicity, or patient refusal to continue with the study or investigator decision to remove the patient from study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumor Response | Objective tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears] or Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline]) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) committee. | From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks | 
| Tumor Response | Tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears], Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline], Stable Disease [SD, steady state of disease], or Progressive Disease [PD, sum of lesion sizes increased at least 20% from smallest sum on study or new lesions]) observed during trial period assessed according to the RECIST committee. | From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control | Disease control was defined as the percentage of participants who had a best response rating of CR (tumor disappears), PR (sum of lesion sizes decreased at least 30% from baseline), or SD (steady state of disease) that was maintained for at least 28 days from the first demonstration of that rating. | From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks | 
| Overall Survival | Overall survival (OS) was calculated as the time from the first date of receiving study medication to death, due to any cause. Participants alive at the time of analysis were censored at their last date of follow-up. | From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). | 
| Progression-free Survival (PFS) | PFS was calculated as time from first date of receiving study drug until date of first observed disease progression (PD) (radiological or clinical, whichever was earlier) or death due to any cause, if death occurred before PD was documented. The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD or death at time of analysis were censored at last date of tumor evaluation. | From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks | 
| Time to Progression (TTP) | TTP was calculated as time from first date of receiving study drug until date of first documented disease progression (PD) (radiological or clinical, whichever was earlier). The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than the scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD at time of analysis were censored at last date of tumor evaluation. | From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks | 
| Duration of Response | Duration of response was defined as the time from the first documented objective response of PR or CR, whichever was earlier, to disease progression or death (if death occurred before progression was documented). Duration of response for subjects who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. | From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks | 
| Duration of Stable Disease (SD) | Duration of SD was calculated as the time from the first date of receiving study drug until the date of documented PD or the last observation if the subject did not progress. Subjects without disease progression at the time of analysis were censored at the last date of tumor evaluation. | From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal Cell Carcinoma