It happened just after 5 p.m. in Brookfield, Wisconsin.
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The driver of that car, a man in his 60s, was killed, but no one on the train was hurt.
Brookfield police said the car had driven around the train crossing gates.
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The train crossing was expected to be closed for several days due to damage.
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Anyone with information on the incident is asked to call Capt. Chris Garcia at the Brookfield Police Department at 262-787-3702.
This is the second time this week that an Amtrak train from Chicago has hit a car on the way to its destination.
Just Wednesday, a train heading to Los Angeles struck a car in Texas.
The driver of the car in that incident also died.