I ride the C&O each year and also live on the DC area. Most efficient use of time is to take the afternoon train on Thursday or Friday to Cumberland and get a room for the night. Air bnb or hotels are plentiful. I ride 20 miles to camp, but since you are not taking a tent, overnighting in Cumberland works well. Then you have three 60 mile days. I usually do it in two days, plus the initial 20 miles, but that makes for long days. Then you end up riding home, which can shorten or lengthen the trip depending on where you live. Nice thing about this is you can pick your weekend with little advance planning depending on the weather forecast and towpath conditions. Just need a bike reservation on Amtrak, but last year they basically stacked around 12 bikes in the bike car.

Note that the road bypass around the Paw Paw Tunnel is a difficult ride. I did it last year and regretted it. Steep hills and unpaved roads make for a slow ride. Not sure whether you are any better off than just using the hiking trail.

As for training, I generally bike commute 150 miles a week and up the mileage to around 200 per week for two weeks prior to riding the canal. My days are 20/90/65.