Vale of Lune were value for a half time lead at Carlisle - but the Cumbrians came back in the second 40 to gain revenge for their defeat at The Lane in the opening fixture of the North Two West campaign.
James Curran opened the Vale's account when he rounded off a well-worked three-quarter move with an unconverted try after seven minutes.
Andy Garnett lashed over a long-range penalty shortly after before the hard working Danny Lin poached a try, which Garnett converted well in the 22nd minute.
Just before half time Carlisle rattled in a try from close range, with two further tries following in the second half, one of which was converted.
Vale's forwards produced a late surge but were unable to break through against a Carlisle defence that hung on.
Vale are in Lancashire Cup action on Saturday when Waterloo visit Powder House Lane in the second round of the county competition.
They will return to North Two West rugby on March 31 when they entertain Broughton Park who are chasing a play off position.
Vale of Lune: A Miller; J Bryan, R Thorn (A Richards 75), J Curran N Bennetts, A Bolsover; P Jackson, D Schuyler, D Halliwell (M Sutcliffe 75); J Knox, D Perry; L Ford (L Farnworth 75), D Lin, M Fowler. * VALE under 16s and under 13s both had plenty to celebrate as they made it through into the EFE Junior Challenge Cup finals.
* The under 13s edged past Liverpool Collegiate on the away rule after the match finished in a 17-17 draw.
* The under 16s, meanwhile, beat Broughton Park 17-7.
The finals take place in Blackpool on Sunday, April 22.
* The under 13s will tackle Preston with the under 16s scrumming down with Tarleton.
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