Clinical Studies

NeoAva – Neoadjuvant Avastin in locally advanced breast cancer

PI: Olav Engebråten           

NeoAva is a multicenter, randomized, phase II clinical trial to evaluate the effect of Avastin (bevacizumab) in combination with neoadjuvant treatment regimens in patients with large primary HER2 negative breast cancers (inclusion ended). For cancers to grow and spread to other organs new blood vessels have to be formed to supplement the tumor with oxygen and nutrients. The NeoAva study examines the effect of the drug bevacizumab that is meant to inhibit the formation of new blood vessels. Tissue biopsies and blood samples were collected before, during and after treatment. Molecular and metabolic characteristics are evaluated with reference to the obtained responses. The comprehensive translational program has resulted in several publications and still ongoing studies

Senior scientist Mads Haugen (PhD) has used machine learning principles to identify a nine-protein signature, the ViRP score, capable to identify patients who benefit from anti-angiogenic treatment with bevacizumab. The protein score is currently being validated in the NAPEER clinical study.

I-BCT -Improved Breast Cancer Therapy in the neoadjuvant and metastatic setting:

PI: Olav Engebråten

I-BCT1 is a randomized, noeadjuvant, phase II clinical study that test the hypothesis of offering additional DNA targeted chemotherapy (carboplantin) to breast cancer patients with an aggressive phenotype (inclusion ended). Patient samples (tumor and blood) were collected before start- and during treatment, and at surgery. A comprehensive translational program including bulk-, single cell- and spatial multi-omics analyses are in progress.

NAPEER - NeoAdjuvant PErsonalized therapy for Estrogen Receptor positive breast cancer

PI: Olav Engebråten

NAPEER is a randomized, neoadjuvant, phase-II study in hormone receptor positive breast cancer. In high-risk patients, chemotherapy starts immediately, while low-risk patients receive neoadjuvant endocrine therapy, randomized to treatment with or without the AKT-inhibitor capivasertib. After 15 days, the endocrine treatment response is assessed by Ki67-expression. Responding patients will continue to receive endocrine/capivasertib treatment, while non-responding patients will be switched to treatment with chemotherapy and randomized to also receive bevacizumab if positive ViRP score. Patients without a positive ViRP signature will be treated with standard chemotherapy.

Tumor biopsies and blood samples are collected longitudinally (before, during, after treatment) and will be subjected to a comprehensive translational program searching for biomarkers by bulk-, single cell- and spatial multi-omics analyses.  

MetAction – Actionable targets in cancer metastasis

MetAction was a project funded through the Research Council of Norway (RCN), program for “Publicly funded clinical studies”, and conducted the first clinical trial in Norway where treatment decisions were based on targeted NGS data. The first part of the study (25 patients) was used to establish the infrastructure needed to be able to offer treatment based on genomic examinations; this included image-guided biopsy sampling, pathological examination, NGS sequencing, bioinformatics pipelines for variant calling and interpretation, molecular- and clinical tumor boards for discussion of molecular data and treatment alternatives. In this first part of the study, we were able only to offer single drug treatment and the samples were screened for mutation in relatively few genes (n=50), and no patients were found eligible for treatment. In the second part of the study, a more comprehensive gene panel was used, consisting of 136 genes, and combination treatment could be offered. Actionable targets were detected in 13/26 patients (15%) and long-term effects were observed in two patients.

The MetAction study demonstrated the feasibility og using targeted NGS to inform on rationale treatment for patients with end-stage metastatic disease. Furthermore, the project established and piloted the diagnostic pipeline and multidisciplinary tumor boards that has been further implemented in the national PCM study IMPRESS.