The following should do the trick, it will exit if the mtime of $file (edit: relative to the script's start time, of course...) is less than zero, ie. $file has been modified after the script's start time:

while (my $cgi = new CGI::Fast ()) {
    # process the current request...
    exit if -M $file < 0;
}
[download]

Then let the webserver take care of restarting it. (Note that the exit call is placed after the processing of a request, since the while loop is only entered after a new request is made to the script, immediate exit could break the connection. This leaves one request being processed with the old settings.)