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Leatherheads, which was directed by Clooney and starred Renée Zellweger, only recouped £18 million and was derided by critics.
"It bombed, and when I say bombed, it bombed," Clooney told Rolling Stone. "Someone said, 'How does that feel?' and it stings a little bit.
"It's not like we just showed up: I was working on this for a couple years and put a lot of work into it, and you get knocked back a little bit."
He added: "The trick is how you handle things when things don't go great. It's easy when things are doing well. The people I most admire are the people who handle it when the studio says 'That's really underperformed' and they say, 'Ow, that hurt'."
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