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

NCT ID: NCT02330783

Last Updated: 2017-05-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2018-12-31

Brief 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.

Detailed 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.

Conditions

Metastatic Renal Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bevacizumab plus Sorafenib

Bevacizumab 5mg/kg Q2w Sorafenib 400mg Bid

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

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

Intervention Type: DRUG

400mg twice daily by oral of each 4-week cycle

Sorafenib

Sorafenib 400mg Bid

Group Type: ACTIVE_COMPARATOR

Sorafenib

Intervention Type: DRUG

400mg twice daily by oral of each 4-week cycle

Interventions

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)

Intervention Type: DRUG

Sorafenib

400mg twice daily by oral of each 4-week cycle

Intervention Type: DRUG

Other Intervention Names

Avstin; Nexavar

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University Cancer Hospital & Institute

OTHER

Sponsor Role: lead

Responsible Party

Jun Guo

Director of department of renal cancer and melanoma

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jun Guo, MD,PHD

Role: PRINCIPAL_INVESTIGATOR

Peking University Cancer Hospital & Institute

Locations

Sun Yat-sen university cancer center

Guangzhou, Guangdong, China

Site Status: NOT_YET_RECRUITING

Peking University First Hospital

Beijing, , China

Site Status: RECRUITING

Beijing Cancer Hospital

Beijing, , China

Site Status: RECRUITING

Cancer Hospital, Fudan University

Shanghai, , China

Site Status: NOT_YET_RECRUITING

Countries

China

Central Contacts

Xinan Sheng, MD

Role: CONTACT

doctor_sheng@126.com

0086-10-88196951

Jun Guo, MD,PHD

Role: CONTACT

guoj307@126.com

0086-10-88196317

Facility Contacts

Fangjian Zhou, MD

Role: primary

zhoufj@sysucc.org.cn

0086-20-87343088

Zhisong He, MD

Role: primary

wyj7074@sohu.com

0086-10-83572211

Xinan Sheng, MD

Role: primary

doctor_sheng@126.com

0086-10-88196951

Dingwei Ye, MD

Role: primary

dwye@163.com

0086-21-64175590

References

Motzer RJ, Porta C, Vogelzang NJ, Sternberg CN, Szczylik C, Zolnierek J, Kollmannsberger C, Rha SY, Bjarnason GA, Melichar B, De Giorgi U, Grunwald 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.

Reference Type: BACKGROUND

PMID: 24556040 (View on PubMed)

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. doi: 10.1158/1078-0432.CCR-06-1975.

Reference Type: BACKGROUND

PMID: 17255307 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18669456 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23598982 (View on PubMed)

Related Links

http://meetinglibrary.asco.org/content/107093-134

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)

Other Identifiers

BCH-RCC-141201

Identifier Type: -

Identifier Source: org_study_id