L11: Clinical trials part 2

Question 1

phase 2

Answer 1

Phase 2 study: general principles
* Short and small-size trials compared to Phase 3

• Endpoints:
  Traditionally: tumor response (complete response, partial response, stable disease or progressive disease) - Binary for objective tumour response (ORR)
  Progression-free survival (PFS) at a fixed point in time
  Toxicity (e.g. grade 3 toxicities over treatment period)
  And time-to-event endpoint (PFS, overall survival OS)
  Combining activity and toxicity

Question 2

one or two-stage designs?

Answer 2

One or two-stage designs
Two-stage allow early stopping if insufficient activity

Single arm or randomized
Choosing primary endpoints for phase 2 studies

appropriate primary endpoint: —-> response —-> monotherapy (single arm), combination (randomised design)

PFS: randomised or single arm

phase 2 is either single arm or randomised. randomised can be non or comparative. comparative: either ‘selection’ pick the winner, randomised discontinuation, randomised phase 2 —> open level or blinded

non c—> reference arm
So in phase 2 you can do just a new drug n tis own and just see what the response rate it but its difficult to compare because e.g: if drug did better than chemo, but since every patient is different you cannot directly say this drug is better than chemo. Whereas if you do a randomised trial you can compare them. But you need more patients, more mone,y mote time.