It's totally doable - and I speak from experience.
The base I started with was a Matrix fanfic series, 20+ stories, a whole swath of original characters, a new spin on some canon elements and some completely new elements.
Three world-builds later, I have an urban fantasy series that bares no resemblance to the stories I started with (other than my own original elements, which weren't dependant on their setting).
It's really hard work, I'll tell you that from the get-go, but it can be really, really rewarding. You will notice, when you go back and read your fanfic, that for instance, you pushed Canon Character A in a certain direction - perhaps within the limitations of their canonical portrayal, sometimes not - run with that new direction, it's one of the very easy steps to help separate your character from the character you've been borrowing.
You may not be able to change genres the way I did, but at least put a new spin on it - the first iteration I did for my original-verse still ran with the "reality isn't reality" angle, but changed it dramatically, from "machines are evil, lol" to an "ark/time-capsule because humanity killed itself off" deal. Whatever your original canon is, there's always a new way to change it, and doing that helps you bring in a lot of new elements, and refine other, smaller elements that you'd already brought to the table.
Another trick is to focus on your original characters, and let canon characters that you don't really have a need for fall away, or - if the canon characters aren't well-explored in canon, and you've added to them, run completely off the elements that you brought to the table.
Invent new characters for an archetype that you need to fill - this helps energise a story, as working with a complete unknown helps you think on your feet about world-building elements that you may not have considered.
PM me if you want to chat.