I thought I was doing ok. Plus I might have just had a revolutionary idea.
And you are. Look, the Borgias had a reputation for poisoning, surely it wouldn't be too difficult for Cesare to do away with Duke Filippo the Landless by means of poison. Filiberto II might put up a fight for a while, and get killed in the fighting. The next heir would be Filiberto's half-brothers, Carlo III, Ludovico and Filippo. If Filippo gets killed by poison or some other, it immediately cuts of there being any more kids of his loins. Filiberto II married twice and had no issue, Carlo waited until 1520 to get hitched and Filippo the same (his took place in the late 1520s).
So, poison Filippo, send Claudine to a convent. That rules out heirs, then you've only got Filiberto, Carlo, Ludovico and Filippo to deal with. Filiberto dies fighting against Cesare as rightful heir, backed by Maximilian I. Ludovico died young, so that could work, which leaves Carlo and Filippo. And considering that both married relatively late in life, there's a lot of space between Carlo II's death in 1496 and Carlo III's marriage in 1521. Especially if Cesare blocks the marriage of Bianca's daughter, Violante to Filiberto, in favor of marrying her to a Borgia-supporter/ally.