Is it Really locked up or is the focus NOW off screen.
That can happen, when you close calibre with 2 monitors and then take one away.
1)easy, connect the 2nd monitor, then move preferences and config dialogs to the main screen before exiting
2)harder. Rename(just in case it does not work) the (hidden) Calibre Configuration folder
Code:
C:\Users\<your logonname>\AppData\Roaming\calibre
Calibre will rebuild THE FACTORY DEFAULT. You lose your settings and plugins