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

Metastatic Renal Cell Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02330783
• Other study ID #: BCH-RCC-141201
• Status: Recruiting
• Phase: Phase 2
• First received: December 29, 2014
• Last updated: May 7, 2017
• Start date: December 2014
• Est. completion date: December 2018

Study information

• Verified date: May 2017
• Source: Beijing Cancer Hospital
• Contact: Xinan Sheng, MD
• Phone: 0086-10-88196951
• Email: doctor_sheng[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 106
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 ß-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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Metastatic Renal Cell Carcinoma

Intervention

Drug:
• Bevacizumab
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)
• Sorafenib
400mg twice daily by oral of each 4-week cycle

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing
China	Peking University First Hospital	Beijing
China	Sun Yat-sen university cancer center	Guangzhou	Guangdong
China	Cancer Hospital, Fudan University	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (4)

Azad NS, Posadas EM, Kwitkowski VE, Steinberg SM, Jain L, Annunziata CM, Minasian L, Sarosy G, Kotz HL, Premkumar A, Cao L, McNally D, Chow C, Chen HX, Wright JJ, Figg WD, Kohn EC. Combination targeted therapy with sorafenib and bevacizumab results in enhanced toxicity and antitumor activity. J Clin Oncol. 2008 Aug 1;26(22):3709-14. doi: 10.1200/JCO.2007.10.8332. Erratum in: J Clin Oncol. 2008 Sep 10;26(26):4363. Figg, William D [added]. — View Citation

Motzer RJ, Porta C, Vogelzang NJ, Sternberg CN, Szczylik C, Zolnierek J, Kollmannsberger C, Rha SY, Bjarnason GA, Melichar B, De Giorgi U, Grünwald V, Davis ID, Lee JL, Esteban E, Urbanowitz G, Cai C, Squires M, Marker M, Shi MM, Escudier B. Dovitinib versus sorafenib for third-line targeted treatment of patients with metastatic renal cell carcinoma: an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Mar;15(3):286-96. doi: 10.1016/S1470-2045(14)70030-0. Epub 2014 Feb 17. — View Citation

Pal SK, Vogelzang NJ. Sequential treatment strategies and combination therapy regimens in metastatic renal cell carcinoma. Clin Adv Hematol Oncol. 2013 Mar;11(3):146-55. Review. — View Citation

Sosman JA, Puzanov I, Atkins MB. Opportunities and obstacles to combination targeted therapy in renal cell cancer. Clin Cancer Res. 2007 Jan 15;13(2 Pt 2):764s-769s. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Safety: adverse events	adverse events	1 years

External Links

•   The BEST trial (E2804): A randomized phase II study of VEGF, RAF kinase, and mTOR combination targeted therapy (CTT) with bevacizumab (bev), sorafenib (sor), and temsirolimus (tem) in advanced renal cell carcinoma (RCC)