Clinical trials Flashcards
The aim of phase 1 studies is what?
- To determine toxicity
2. To establish maximum tolerated dose (MTD)
Are drugs with no clinically activity rejected in phase 1?
No - disease response is not an endpoint, so drugs with no clinical activity are not rejected at this stage
What does LD10 mean?
10% of the dose that is lethal in 10% of mice - dose escalation is performed using this
How is dose escalated and toxicity measured?
3 patients are treated at each dose level until side effects are seen, and then 6 patients per group until the maximum tolerated dose is reached
What patients are suitable for phase 1 trials?
Patients with any tumour, in whom no conventional therapy is appropriate. Patients must remain generally fit and in particular have near normal renal and hepatic function
Are phase 1 trials randomized or comparative?
no
What is the aim of phase 2 trials?
To assess the particular anti-tumour activity of a new treatment in a range of different cancers chosen based upon the scientific knowledge of the cancer and the drug
What is the primary outcome measured in phase 2 trials?
the response rate (shrinkage of the tumour)
do you need a control arm and random allocation in all phase 2 trials?
no - but can be useful as provides a guide to patients selection, avoids criticism of undue case selection
What is the purpose of phase 3 studies?
conclude if a treatment is an improvement upon existing options
What study design do phase 3 studies normally take?
randomised controlled trials to compare with established treatments
What are the common primary end points in phase 3 studies?
The length of life whatever the cause of death (overall survival)
or the length of life until the cancer grows (progression-free survival)
What are common secondary end points in phase 3 trials?
radiological shrinkage (response rate) quality of life
Why do phase 3 trials often need multicentres?
Need more patients for better statistical significance
How is survival data generally presented?
Kaplan meier curves
