This study tries to evaluate the role of chemoradiation with capecitabine and bevacizumab in oligometastatic patients neither being progressive nor resectable after chemotherapy.
Combining chemoradiation with an antiangiogenic agent has a strong biological rationale, and preclinical studies consistently show an increase in radiosensitization with combined treatment. It is well described that hypoxia or HIF-1 expression is associated with a lower radiation response and progression in solid tumors. Radiation itself induces transient tumor hypoxia, which in turn stimulates VEGF production and VEGFR-2 expression what may also serve as a paracrine proliferative stimulus that promotes out-of-field growth. The combination of radiotherapy with an antiangiogenic agent (e.g. bevacizumab) thus offers the potential to enhance the effect of radiation, and avoid further spread of disease. Furthermore, targeting tumor vasculature improves the delivery of cytotoxic drugs (e.g. capecitabine) leading to increased efficacy of chemoradiation. Combination with cytotoxic drugs could additionally limit treatment-induced hypoxia (Senan and Smit 2007; Mazeron, Anderson et al. 2011).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
1
825mg/m2 per os bid
7.5 mg/kg
(conventional or intensity-modulated and image-guided radiotherapy)
University Hospital Hamburg-Eppendorf
Hamburg, Germany
Progression free survival rate
Progression free survival rate at 12 months after start of induction treatment (PFSR@12)
Time frame: 12 months
Time to progression (TTP) in 2 cohorts
Time to progression (TTP) in 2 cohorts: 1. regards only progression within (TTPir) and 2. in- and outside irradiated areas ("overall" TTP)
Time frame: 24 months
Overall Response Rate
Efficacy of the investigational therapy shown by the Overall Response Rate (CR and PR) according to RECIST v1.1
Time frame: 12 months
Overall survival (OS)
Time frame: 36 months
Quality of life (QoL)
Quality of life using the EORTC QLQ-C30 and the module CR29
Time frame: 12 months
Prognostic and predictive value of PET scan
Prognostic and predictive value of PET scan at baseline and at 2 months after chemoradiation
Time frame: at baseline and 2 months after chemoradiation
Toxicity
Number of adverse events, according to NCI CTCAE v4.0)
Time frame: 12 months
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