Most browsers will cache modules returned via RequireJS, which is how Durandal obtains its modules and view models.
CTRL+F5 doesn't help because that just refreshes the initial page - all the modules are still requested using javascript (RequireJS), so they are usually pulled from cache first.
I've found it's best to disable caching in your browser's developer tools. Doing so will ensure that all network requests are loaded directly from the source and not from cache.
See this question for additional information: Debugging when using require.js cache
Another solution is configure RequireJS to set its urlArgs
property: https://stackoverflow.com/a/8479953/91189
This solution works ok, but makes it harder to debug, at least in Chrome, because breakpoints are lost every time the module is loaded, since it's technically a different file being requested each time.