Phase III Ascentar (NOVC) Study Halted - Ineffective Drug or Faulty Trial Design?

Implications: Prior studies had suggested an improvement in survival when calcitriol was added to weekly docetaxel. The premature closure of this study ocurred due to an increased death rate in patients receiving the combination of weekly docetaxel compared to q 21 day docetaxel. Faulty trial design, and not necessarily inactivity of the drug, may be to blame for this. Competing trials in this space include the Docetaxel Plus GVAX phase III (Cell Genesys) and the Docetaxel plus Bevacizumab phase III study (US Cooperative Group/Genentech) 

Analysis: The major flaw of this trial was that the treatment arm (with docetaxel plus calcitriol) used weekly docetaxel, which has been shown to be inferior, in terms of survival, to q21 day docetaxel - Based on the Tax 327 study. Therefore, it is not certain whether the negative results of this trial stem from the inactivity of calcitriol or the weekly versus q21 day docetaxel inequalities. That said, it is unlikely that a study of q21 day docetaxel plus/minus calcitriol will be performed anytime soon. Thus, the inequalities of the controls in this study may have been a fatal flaw for Ascentar. Toxicity will be interesting to see because there is a suggestion that calcitriol reduces thrombosis and overall toxicity of the chemotherapy but that point may no longer be relevant. Phase III results from the Avastin plus Docetaxel study and the GVAX plus Docetaxel Study are anticipated.