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Prospective Study of VEGFR-2 /IL-8 Genetic Interaction in MBC Treated With Paclitaxel and Bevacizumab vs. Chemotherapy (BEVAPROS)

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ClinicalTrials.gov Identifier: NCT02329639
Recruitment Status : Recruiting
First Posted : December 31, 2014
Last Update Posted : October 25, 2017
Sponsor:
Information provided by (Responsible Party):
Guido Bocci, University of Pisa

Tracking Information
First Submitted Date December 29, 2014
First Posted Date December 31, 2014
Last Update Posted Date October 25, 2017
Study Start Date April 2014
Estimated Primary Completion Date March 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: December 31, 2014)
Progression free survival [ Time Frame: 24 months ]
progression free survival in an unselected population of metastatic breast cancer patients treated with first-line paclitaxel and bevacizumab or with chemotherapy alone, assessed through the multifactor dimensionality reduction methodology (genetic interaction analysis)
Original Primary Outcome Measures
 (submitted: December 29, 2014)
Progression free survival [ Time Frame: 24 months ]
progression free survival in an unselected population of metastatic breast cancer patients treated with bevacizumab combined with first-line paclitaxel assessed through the multifactor dimensionality reduction methodology (genetic interaction analysis)
Change History Complete list of historical versions of study NCT02329639 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: December 31, 2014)
Overall survival [ Time Frame: 24 months ]
overall survival in an unselected population of metastatic breast cancer patients treated with first-line paclitaxel and bevacizumab or with chemotherapy alone, assessed through the multifactor dimensionality reduction methodology (genetic interaction analysis)
Original Secondary Outcome Measures
 (submitted: December 29, 2014)
Hormonal-receptor status [ Time Frame: 24 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Prospective Study of VEGFR-2 /IL-8 Genetic Interaction in MBC Treated With Paclitaxel and Bevacizumab vs. Chemotherapy
Official Title Prospective Evaluation of VEGFR-2 rs11133360/IL-8 rs4073 Genetic Interaction in Metastatic Breast Cancer Patients Treated With Paclitaxel and Bevacizumab vs. Chemotherapy Alone (BEVAPROS)
Brief Summary Metastatic Breast cancer (MBC) patients from ten Italian Divisions of Medical Oncology, with histologically confirmed HER2-negative MBC, treated with a first-line therapy including bevacizumab 10 mg/m2 i.v. on days 1 and 15 combined with first-line paclitaxel 90 mg/m2 i.v. on days 1,8 and 15, every 4 weeks, will be enrolled for the present pharmacogenetic study. MBC patients treated with first-line chemotherapy including paclitaxel without bevacizumab will be also enrolled as control group.
Detailed Description Metastatic Breast Cancer (MBC) patients from ten Italian Divisions of Medical Oncology, with histologically confirmed HER2-negative MBC, treated with a first-line therapy including bevacizumab 10 mg/m2 i.v. on days 1 and 15 combined with first-line paclitaxel 90 mg/m2 i.v. on days 1,8 and 15, every 4 weeks, will be enrolled for the present pharmacogenetic study. MBC patients treated with a first-line chemotherapy without bevacizumab will be also enrolled as control group. Sites of metastatic disease will be radiologically re-evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1, in patients with measurable disease. In patients without measurables lesions, progression of disease will be defined when new lesions appeared or when existing lesions evolved. In the case of non measurables lesions, deterioration of clinical condition not due to treatment toxicity, will be defined as progression disease. Progression-free survival (PFS), will be defined as the period of time from the beginning of the treatment to the first observation of disease progression as above described, or death from any cause. All patients will be for response, PFS and overall survival. Each patient entering the study will sign the informed consent. The protocol has been approved by Ethics Committee Vast Area Northwest of Tuscany (CEAVNO), Pisa, Italy (30/04/2014). Genotyping analyses blood samples (3 ml.) will be collected in ethylenediaminetetraacetic acid tubes and stored at -80° C. Genes and polymorphisms involved in the angiogenesis pathway and already suggested as predictors of bevacizumab response, will be chosen for the present analyses. Germline DNA extraction will be performed using QIamp DNA Blood Mini Kit (Qiagen, Valencia, California, USA). Allelic discrimination of genes will be performed using an ABI PRISM 7900 SDS Instrument (Applied Biosystems, Carlsbad, California, USA) and with validated TaqMan single nucleotide polymorphism (SNP) genotyping assays (Applied Byosistems). Polymerase chain reactions will be carried out according to the manufacturer's protocol. Genotyping will be not performed until an adequate number of events (>80% on study population) will be reported in terms of PFS. Statistical analysis: The first aim of this prospective analysis will be evaluate the possible role of VEGFR-2 rs11133360/IL-8 rs4073 polymorphism genetic interaction to predict the bevacizumab response in terms of PFS. The secondary end-points will be the correlations with overall survival (OS) and response rate. All polymorphisms will be analyzed for deviation from the Hardy-Weinberg Equilibrium (HWE) by means of comparison between observed allelic distributions with those expected from the HWE by on x2 test. Any correlation between gene polymorphisms and response rate will be analyzed by the two-sided Fisher's Exact Test. The association between each individual polymorphism and the most relevant clinical-pathological characteristics with PFS will be tested using a Cox proportional hazards model. The Multifactor Dimensionality Reduction (MDR) methodology will be applied (using version 2.0 beta 6 of MDR software available on http://sourceforge.net/projects/mdr/) to investigate the role of an interaction between gene polymorphisms in identifying biomarkers of paclitaxel plus bevacizumab response. The genotype combination with the highest PFS benefit correlated with an OS improvement will be chosen for further analyses. The difference in PFS between favourable genetic profiles and the unfavourable genetic profiles will be assessed with the log-rank test and the kaplan-Meier method to evaluate survival curves. A Cox proportional hazards model, with the possible genetic profiles and the clinical and pathological patient characteristics individually correlated with the PFS, will be used to calculate the adjusted hazards ratio (HR) and the 95% confidence interval (95% CI). A P value of<0.05 will be accepted as statistically significant. Tha Kaplan-Meier and Cox proportional hazards analyses will be performed using the SPSS version 17.0 (SPSS, Chicago, IL).
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
whole blood
Sampling Method Non-Probability Sample
Study Population MBC patients treated with a first-line chemotherapy including paclitaxel with or without bevacizumab
Condition Metastatic Breast Cancer
Intervention Genetic: genetic interaction analysis
VEGFR-2 rs11133360/IL-8 rs4073 genetic interaction analysis
Study Groups/Cohorts
  • case group
    genetic interaction analysis of women with HER2 negative metastatic breast cancer performing a first-line chemotherapy with bevacizumab
    Intervention: Genetic: genetic interaction analysis
  • control group
    genetic interaction analysis of women with HER2 negative metastatic breast cancer performing a first-line chemotherapy without bevacizumab
    Intervention: Genetic: genetic interaction analysis
Publications * Allegrini G, Coltelli L, Orlandi P, Fontana A, Camerini A, Ferro A, Cazzaniga M, Casadei V, Lucchesi S, Bona E, Di Lieto M, Pazzagli I, Villa F, Amoroso D, Scalese M, Arrighi G, Molinaro S, Fioravanti A, Finale C, Triolo R, Di Desidero T, Donati S, Marcucci L, Goletti O, Del Re M, Salvadori B, Ferrarini I, Danesi R, Falcone A, Bocci G. Pharmacogenetic interaction analysis of VEGFR-2 and IL-8 polymorphisms in advanced breast cancer patients treated with paclitaxel and bevacizumab. Pharmacogenomics. 2014 Dec;15(16):1985-99. doi: 10.2217/pgs.14.140.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: December 29, 2014)
189
Original Estimated Enrollment Same as current
Estimated Study Completion Date July 2018
Estimated Primary Completion Date March 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • histologically confirmed HER2-negative MBC, treated with a first-line therapy including bevacizumab 10 mg/m2 i.v. on days 1 and 15 combined with first-line paclitaxel 90 mg/m2 i.v. on days 1,8 and 15,every 4 weeks, will be enrolled for the present pharmacogenetic study. MBC patients treated with a first-line chemotherapy without bevacizumab will also be enrolled as control goup.

Exclusion Criteria:

  • histologically not confirmed HER2-negative MBC, and patients not treated with a first-line chemotherapy with or without bevacizumab.
Sex/Gender
Sexes Eligible for Study: Female
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Giacomo Allegrini, MD +39-0587-273104 g.allegrini@usl5.toscana.it
Contact: Guido Bocci, MD, PhD +39-050-2218756 guido.bocci@med.unipi.it
Listed Location Countries Italy
Removed Location Countries  
 
Administrative Information
NCT Number NCT02329639
Other Study ID Numbers University of Pisa - Az. USL 5
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Guido Bocci, University of Pisa
Study Sponsor University of Pisa
Collaborators Not Provided
Investigators
Principal Investigator: Guido Bocci, MD, PhD Dept. of Clinical and Experimental Medicine, University of Pisa
PRS Account University of Pisa
Verification Date October 2017