Thanks to his uncle's protection he was appointed to the College of Cardinals on 16 May 1288, receiving from the then Pope Nicholas IV the title of cardinal-deacon S. Eustachio.
In 1297 a conflict broke out between Pope Boniface VIII and the family Colonna, that was allied with the French King Philip IV of France.
In response, they announced a manifest blaming Boniface VIII for the death of his predecessor Pope Celestine V and the unlawfulness of his election.
After the death of Boniface, VIII Pietro and Giacomo were excluded from participation in the election of a successor due to the excommunications that were imposed on them.
The then elected Pope John XXII granted him the titular church of S. Angelo in Pescheria (2 March 1317) and appointed him Archpriest of the Basilica of S. Maria Maggiore on 16 August 1318.