Clinical trial NCT02330783: Efficacy and Safety of Bevacizumab Plus Sorafenib for the Third-line Treatment in Metastatic Renal Cancer Patients
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Renal Cell Carcinoma
Keywords: Metastatic Renal Cell Carcinoma
Third-line treatment
Sorafenib
Bevacizumab
Lead sponsor: Peking University Cancer Hospital & Institute
Sponsor class: OTHER
First posted: 2015-01-05
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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
  * Other conditions unsatisfying the inclusion criteria in the investigator's opinions

Primary outcomes:
measure: progress-free survival,PFS
timeFrame: 2 years
Secondary outcomes:
measure: overall survival,OS
timeFrame: 3 years
measure: Safety: adverse events
timeFrame: 1 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen university cancer center
state: Guangdong
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Shanghai
country: China
facility: Cancer Hospital, Fudan University
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Jun Guo, MD,PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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. doi: 10.1158/1078-0432.CCR-06-1975.
citation: 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.
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.