Simple - Destroy Sigil.
How? Destroy the Spire.
According to MotP, magic is impeded and limited near the Spire. At 1,200 miles, you can use any spell you wish. This is all according to the chart and text on page 147.
So... as an epic caster of no small power, stand 1,200 miles away (or less, where high-level magic is impeded - Spellcraft check of 35 needed to cast). Create an epic spell, destroy the Spire with it. Simple.
You could argue the Spire mutes magic that enters the area. No such mechanic exists in 3E, to my knowledge, though it is certainly logical.
Another alternative way is to simply use technology - it's not muted at all. epic-level fighters with explosives could eventually chip away enough of the Spire for it to topple. Plus, they'll be the best equipped to deal with pesky interlopers - according to MotP, few divine powers even work near the spire, so certainly no mortal magic would. Only a major god could stop you, and even then I'd rule their powers severly limited - as per the rules laid out in MotP.
Of course, you could just hand-wave it, since that's exactly what the Lady of Pain is - a hand-wave. A convenient plot device that "explains" why no gods are involved. It's the only thing I didn't like in Planescape.
Note, destoying the Spire would cause a major cataclysm, since it's supposedly the axis of the planes.