A phase I study of the combination of ro4929097 and cediranib in patients with advanced solid tumours (PJC-004/NCI 8503)

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 Background: 

The Notch signalling pathway has been implicated in tumour initiation, progression, angiogenesis and development of resistance to vascular endothelial growth factor (VEGF) targeting, providing a rationale for the combination of RO4929097, a γ-secretase inhibitor, and cediranib, a VEGF receptor tyrosine kinase inhibitor.

"This was an open-label, dose escalation phase I trial. It followed the standard 3+3 rule and no intra-patient dose escalation was allowed. Initial design of study consisted of two stages: (1) dose escalation and (2) expansion cohort, including patients with breast cancer, malignant melanoma, colorectal cancer, pancreatic cancer, renal cancer, high-grade glioma, non-small cell lung cancer, or ovarian cancer. However, accrual was terminated on 7 April 2012, after completion of three dose levels (DLs), due to discontinuation of RO4929097 development. Patients who were felt to be deriving clinical benefit were allowed to remain on cediranib monotherapy on study. The trial was approved by all relevant institutional ethical committees.....