Using burst spells, such as the destiny Energy burst or Dragon Breath in rooms that spawns waves (for the big guy to arrive) 'kills' subsequent waves from the same spots and breaks the wave going forward and the doors don't unlock. That also applies to spells like implosion.
Also, breaking root barriers with spells or runearms causes the waves to stop spawning. This can be seen in the third big guy room in the basement, where if you break the root barrier with spells or rune arm the critters will just stand there doing nothing.