A homebrew campaign or setting is no different than pre-published one in any substantive way. Treat it however you'd treat that. Generally speaking no matter how you're running things simply generating plot hooks generally shouldn't require massive revisions of the surrounding framework. In fact I'm struggling to even think of how such a situation would be at all possible.

What exactly is the situation your players are in, what are their motivations & goals and how do they fit within the current context of the setting? If we knew that it'd be possible to get into specifics that relate to your actual situation at the table.