Polymorphism Interaction to Predict Bevacizumab Efficacy

NCT01935102 | Completed DMC

• 2 other identifiers: CESM3077/2010AIRC-IG9164
• Study Type: observational
• Target: 169
• Locations: 1 country
• Sites: 1

Brief Summary

Although many attempts have been done to identify vascular endothelial growth factor-A (VEGF-A) single nucleotide polymorphisms (SNPs) correlated with bevacizumab response, in advanced cancer patients, the results are still inconclusive. We will conduct a pharmacogenetic study to assess, in a population of metastatic breast cancer (MBC) patients, the possible predictive role of VEGF-A, VEGF receptor-2 (VEGFR-2), interleukin-8 (IL-8), hypoxia inducible factor-1α (HIF-1α), hypoxia inducible factor-2α (HIF-2α) and thrombospondin-1 (TSP-1) SNPs for bevacizumab response when combined with first-line paclitaxel and for progression free survival (PFS). Analyses will be performed on germline DNA obtained from blood samples and SNPs will be investigated by real-time polymerase chain reaction (PCR) technique. The multifactor dimensionality reduction (MDR) methodology will be applied to investigate the interaction between SNPs.

Conditions

Metastatic Breast Cancer

Keywords

metastatic breast cancer; bevacizumab; single nucleotide polymorphism; VEGF-A; VEGFR-2; IL-8

Outcome Measures

Primary Outcomes (1)

• progression-free survival

  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

  24 months

Secondary Outcomes (1)

• Hormonal-receptor status

  24 months

Study Arms (2)

Chemotherapy

MBC patients treated with a first-line chemotherapy including paclitaxel without bevacizumab

bevacizumab+chemotherapy

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

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

metastatic breast cancer patients from eight Italian divisions of Medical Oncology

You may qualify if:

• diagnosis histologically confirmed of metastatic breast cancer
• age (from 18 to 90 years)
• Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1-2)
• hormonal-receptor status (positive or negative)
• previous adjuvant chemotherapy (none, anthracycline or anthracycline plus taxane)
• previous hormonal therapy (adjuvant or metastatic)disease-free interval from the first diagnosis of breast cancer (≤ or \>12 months)
• extent of disease (≤ or \>3 sites)
• location of disease (viscera or bone)
• disease evaluation (measurable or non-measurable)and bevacizumab maintenance (yes or no).

You may not qualify if:

• Patients with human epidermal growth factor receptor type 2 (HER2)-positive

Sponsors & Collaborators

• University of Pisa: lead

Study Sites (1)

Department of Clinical and Experimental Medicine, University of Pisa

Pisa, I Am Not in the U.S. Or Canada, 56125, Italy

Location

Related Publications (5)

• Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007 Dec 27;357(26):2666-76. doi: 10.1056/NEJMoa072113.

  PMID: 18160686 BACKGROUND

• Miles DW, Chan A, Dirix LY, Cortes J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, Harbeck N, Steger GG, Schneeweiss A, Wardley AM, Chlistalla A, Romieu G. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010 Jul 10;28(20):3239-47. doi: 10.1200/JCO.2008.21.6457. Epub 2010 May 24.

  PMID: 20498403 BACKGROUND

• Schneider BP, Wang M, Radovich M, Sledge GW, Badve S, Thor A, Flockhart DA, Hancock B, Davidson N, Gralow J, Dickler M, Perez EA, Cobleigh M, Shenkier T, Edgerton S, Miller KD; ECOG 2100. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol. 2008 Oct 1;26(28):4672-8. doi: 10.1200/JCO.2008.16.1612.

  PMID: 18824714 BACKGROUND

• Pander J, Wessels JAM, Gelderblom H, van der Straaten T, Punt CJA, Guchelaar HJ. Pharmacogenetic interaction analysis for the efficacy of systemic treatment in metastatic colorectal cancer. Ann Oncol. 2011 May;22(5):1147-1153. doi: 10.1093/annonc/mdq572. Epub 2010 Nov 3.

  PMID: 21048041 BACKGROUND

• 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.

  PMID: 25521357 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

whole blood

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Guido Bocci, MD, PhD

  University of Pisa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 26, 2013
• First Posted: September 4, 2013
• Study Start: December 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2014
• Last Updated: December 2, 2014

Record last verified: 2014-12

Locations

IT (1)