Blue Book: Clinical Trails

Question 1

What are the aims of a Phase 1 Clinical Trail?

Answer 1

Determine toxicity (previously tested in vitro/in animals) and establish the maximum tolerated dose.

In general, 3 patients are treated and dose escalation is performed from 10% of dose to that was lethal in 10% of mice.

Patients with any tumour, in whom no conventional therapy is appropriate.

Question 2

Phase 2?

Answer 2

Anti-tumor acitivty in a range of cancers. The radiological tumour shrinkage (response rate) is the primary measure.

Is it an improvement to existing options?

Question 3

Phase 3?

Answer 3

Randomised trails comparing new with established treatment. Endpoints:

Question 4

What measurements can be used to assess tumor response?

Answer 4

Tumor growth/shrinkage: radioloigcally, measure the longest diameter (LD).

Complete response: disappearance
Partial response: 30% decrease in LD.
Progression: 20% increase in LD
Stable disease: Neither shrinkage or increase.

Frequently patients cannot be classified to lack of data, follow up, withdrawal or death. If exlcude= bias.
Final analysis should be intention to treat basis.

Question 5

How to measure survival?

Answer 5

Overall survival: length of time between entry to trail and death of any cause.

Disease free survival: time between entry to trail and recurrence of tumour or death.

Time to progression: time between entry to trial and disease progression or recurrence.

Question 6

What else can be measured?

Answer 6

Toxicity using WHO toxiticity criteria.

QoL

Question 7

Discuss:
Randomisiation.
Number of patients
Survival curves

Answer 7

Randomisation: reduce bias, maybe aware of treatment or blinded.

N.O.P: determined by size of effect and statistical significance. Small effect, high significance= large. Big effect (20% response rate) few patients (14) required.

Survival curves: probability of survival against time. Medical survival and survival rate at 5 years can be estimated.