Neo-Ava: A multicenter, randomized, phase II clinical trial to evaluate the effect of Avastin (bevacizumab) in combination with neoadjuvant treatment regimens on the molecular and metabolic characteristics and changes in the primary tumors with reference to the obtained responses in patients with large primary HER2 negative breast cancers.
Despite the improved results obtained by more aggressive and individual response tailored therapy, breast cancer patients with large tumors still have a less favourable outcome compared to patients diagnosed with smaller tumors. Whether antiangiogenic treatment strategies as bevacizumab may improve the tumor response and eventually the prognosis for these patients, is not known. The role of such treatment in combination with endocrine therapy has not been evaluated in these patients, but is of interest to explore.
This project integrates randomized neoadjuvant treatment with bevacizumab in locally advanced breast cancer and a detailed analysis of the breast cancer disease in the patients. Knowledge of how such treatment combinations influences the gene expression profiles, metabolomics and the signaling pathways in the tumor cells may be of significant impact for the interpretation of the treatment results in patients. In the event of treatment resistance and failures, such analyses can give clues to the possible responsible mechanisms for this outcome, and be used as guidelines for further development of viable therapeutic strategies. In addition, angiogenic gene expression profiles and signaling pathway signatures in responding tumors may assist in the selection of patients for such treatment.
The primary objective is to determine the molecular and metabolic characteristics in addition to dynamic MRI characteristics in the primary tumors with reference to the obtained response (pathological complete response and clinical objective response) by treatment with chemotherapy +/- bevacizumab or endocrine therapy +/- bevacizumab as preoperative (neoadjuvant) treatment in HER2-negative patients. The molecular and metabolic characteristics and changes in the primary tumors will be evaluated by analyses of tumor samples taken before, under and after the treatment period (at surgery) using SNP, CGH and gene expression profiling in addition to proteomic/kinase array profiling and metabolomics using high resolution MR magnetic angle spinning (HR-MAS) analyses.
PI: Olav Engebråten, Oslo University Hospital.