If a target is attacked, while under the influence of any sort of "Calm" spell, it will automatically break them out of the power of the spell. No second RR, they are immediately freed from of the spell the moment that the attack is initiated (i.e. they get to defend themselves).
Being the subject of a Calm-inducing spell will NOT, in any way, affect the ability of the targeted character/creature to defend itself from an attack (no minuses to parrying).
Targets in combat - this is more up to the GM as to whether or not the spell would work. I would recommend that the target get a +50 to RR while in combat (as the spell is trying to impose one extreme from the far end of the other extreme).
Something to keep in mind though -- Regardless of that RR, if the target is in combat, this means that they are likely fighting somebody and if the caster gets his spell off before the target's foe attacks that round, there is a very good chance that even if the spell does affect the target, the foe's incoming attack is just going to negate it anyways.
This makes Calm spells good for preventing combat, not stopping it.
