I recently came across a Chrome issue which I think is worth sharing it with you.
I worked on a self written API using an HttpHandler which primary should return jso
I was running into this error when generating a file and pushing it to the user for download, but only occasionally. When it didn't fail, the file was consistently 2 bytes short. Close() forcibly closes the connection, whether it's finished or not, and in my case it was not. Leaving it out, as suggested in the question, meant the resulting file contained both the generated content as well as the HTML for the entire page.
The solution here was replacing
context.Response.Flush();
context.Response.Close();
with
context.Response.End();
which does the same, but without cutting the transaction short.