Efficacy and Safety of Bevacizumab Plus Sorafenib for the Third-line Treatment in Metastatic Renal Cancer Patients

Study Overview
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Brief Summary
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There is no standard treatment in patients with renal cell carcinoma that was previously treated with VEGF targeted therapies and mTOR inhibitors.So investigators conducted a randomized, open-label, multi-center phase II study to compare bevacizumab plus sorafenib versus sorafenib for the third-line treatment of patients with Metastatic renal cell carcinoma.

Detailed Description
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Therapies targeting VEGF and mTOR signalling pathways represent standard first-line and second-line treatment options for patients with metastatic renal cell carcinoma. There is no standard treatment in patients with renal cell carcinoma that was previously treated with VEGF targeted therapies and mTOR inhibitors.To the best of the investigators knowledge, GOLD study is the first phase 3 trial in the third-line setting after both VEGF-inhibitor and mTOR-inhibitor drugs.From this study,Sorafenib may be option for the third-line treatment.The Best trial demonstrated that Bevacizumab/sorafenib had best efficacy in advance renal cancer canrcinoma and the VEGF/VEGFR co-inhibition strategy may warrant further investigation possibly with more selective VEGFR inhibitors.So investigators conducted a randomized, open-label, multi-center phase II study to compare bevacizumab plus sorafenib versus sorafenib for the third-line treatment of patients with Metastatic renal cell carcinoma.

Official Title
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A Randomized, Open-label, Multi-center Phase II Study to Compare Bevacizumab Plus Sorafenib Versus Sorafenib for the Third-line Treatment of Patients With Metastatic Renal Cell Carcinoma

Conditions
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Metastatic Renal Cell Carcinoma

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≥18 years, ≤75 years, male or female Advanced renal cellcarcinoma is diagnosed histologically or pathologically 1st line treatment of Sunitinib and 2nd line treatment of Everolimus and no more systemic anti-angiogenesis targeted drug therapy Have at least one measurable tumor lesion (Response Evaluation Criteria In Solid Tumors) Eastern Cooperative Oncology Group（ECOG) performance scale is 0 or 1 The expected life span is ≥12 weeks No contraindications for chemotherapy, with enough liver function and renal function and normal ECG recording Peripheral hemogram: neutrophil≥1.5×109/L, Plt≥100×109/L, Hgb≥90g/L Renal function: serum creatinine≤1.5 folds the upper limit of normal (ULN) For patients with non-metastatic liver dysfunction:alanine aminotransferase and aspartate aminotransferase≤2.5 ULN, For patients with metastatic liver dysfunction: alanine aminotransferase and aspartate aminotransferase≤5 ULN The patients participate voluntarily and have signed the informed consent form Exclusion Criteria: Pregnant and lactating women, or female patients of child-bearing age without taking contraceptive measures Patients with severe acute infection without being controlled effectively or having pyogenic and chronic infections with persistently unhealed wounds Past history of serious heart diseases, including: cardiac function classification ≥NYHA class II, unstable angina pectoris, myocardial infarction, arrhythmia requiring anti-arrhythmic drug therapy (excluding β-blockers or digoxin), and uncontrolled hypertension Patients with a history of HIV infection or active phase of chronic hepatitis B/C negative imaging examination result 4 weeks prior to enrollment) Epilepsy patients requiring drug therapy (e.g. steroids or antiepileptic drugs) A history of allogeneic organ transplantation Patients with evidence of hemorrhagic constitution or a past history of hemorrhage Patients currently receiving renal dialysis Past or present concomitant tumors with the primary lesions or histological characteristics different from the tumors evaluated in this study, excluding other tumor cured longer than 3 years before enrollment Patients participating in other clinical trials simultaneously Other conditions unsatisfying the inclusion criteria in the investigator's opinions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab plus Sorafenib<br>Bevacizumab 5mg/kg Q2w Sorafenib 400mg Bid | Drug: Bevacizumab<br>* 5mg/kg by intravenous (IV) infusion every two weeks of each 4-week cycle (dose was based on patient's weight at screening and remained the same throughout study)<br>* Other names: Avstin;Drug: Sorafenib<br>* 400mg twice daily by oral of each 4-week cycle<br>* Other names: Nexavar;|
| Active Comparator: Sorafenib<br>Sorafenib 400mg Bid | Drug: Sorafenib<br>* 400mg twice daily by oral of each 4-week cycle<br>* Other names: Nexavar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progress-free survival,PFS | Time from enrollment to the dates of disease progression,death from any cause or last tumor assessment reported between date of first patient enrollment until 31 December 2017 cut of date | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival,OS | Time from enrollment to the dates of death from any cause or last follow up reported between date of first patient enrollment until 31 December 2017 cut of date | 3 years | 
| Safety: adverse events | adverse events | 1 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Renal Cell Carcinoma, Third-line treatment, Sorafenib, Bevacizumab