I've hit this a few times. From memory, what you need to do in the editor is:
- Rename the current file that displays what calibre thinks is the cover is so that it is not "title_page.xhtml". In the file browse, this is shown with an icon.
- Rename the current cover image in the book so that it is not "cover".
- Add the new cover image.
- Right-click on the new image and select "Mark as cover image".
- Add an new text file. The contents do not matter.
- Mark the new text file as the cover.
- Open the "Add cover" tool.
- Select the new cover image added above as the cover and press OK.
I think each time I have done it, I have done it in a slightly different way, and have needed backout and start again. But, I think these are what I have just done with a test book. They should leave the book with the correct cover and in a state where if you update the cover in the metadata editor, calibre can save it to the book properly.