The preliminary investigation shows that a blue 2013 Chevrolet Cruze, which was traveling northbound on I-65 near mile marker 240, ran off the roadway for an unknown reason, Indiana State Police said.
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The vehicle then struck a large tree, which caused the vehicle to come to a stop and catch on fire.
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Witnesses at the scene were able to remove the driver from the wreckage but were unable to get the passenger out before the vehicle became fully engulfed in flames, police said.
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Both the driver and passenger were pronounced dead at the scene by the Lake County Coroner's Office.
Three dogs were also in the vehicle and died as a result of the crash, police said.
The identity of the victims has not yet been released.