They just need to erase the entirety of it. If the void that cream/hand uses grants instant death, then as long as the entire object is placed inside, then it won't be able to revive. They can either engulf it one attack or deliver multiple attacks, as long as all parts disappear.
Hm what could be able to kill B.I.G? D4C if its a small one since he can bring another B.I.G to explode it if The other dimensions had stands,The hand can kill a small one,Cream can kill a medium sized one and D4C (Love Train)If it can put damage back to B.I.G then maybe it can kill a medium sized B.I.G.This is just my opinion