overview of clinical research in oncology

Question 1

clinical trials

Answer 1

experiments to determine value of treatment

Question 2

no matter how good your pre-clinical data is you cannot?

Answer 2

predict drug will work in human beings

Question 3

what are the 2 key components of clinical trials?

Answer 3

(1) results are required to support conclusion instead of reasoning
(2) experiments must be planned and conducted under controlled conditions to give definitive answers to well defined questions. If not done right, you will not get right answer.

Question 4

in essence what is a protocol?

Answer 4

explains what you want to do and how do you want to test drug

Question 5

protocol defines?

Answer 5

question to be answered
number of patients needed to answer question
treatment and evaluation of a well defined set of patients

Question 6

why does drug have to be tested on healthy patient?

Answer 6

to see result of drug without any other factors interfering with it

Question 7

performance status that patient must have for clinical trials

Answer 7

70% or above
70% you are home and can take care of yourself
must be self dependent

Question 8

patient inclusion criteria for clinical trials?

Answer 8

must have good kidney function
good hepatic (liver) function
good heart function
good hematopoietic function
basically good function of vital organs

Question 9

patient exclusion criteria for clinical trials

Answer 9

any chronic infections
no HIV
no other type of cancer
no other malignancies
pregnancy, lactating, gyn complications
if drug tested interacted with other drug on market

Question 10

what is the scientific key to clinical trials?

Answer 10

the statistics

Question 11

research

Answer 11

systematic investigation including research development, testing and evaluation to develop or contribute to generalized knowledge

Question 12

human subject

Answer 12

living (no autopsy) individual that an investigator conducting research obtains data through intervention with individual or identifiable private information

Question 13

patient have the right to withdraw as stated in informed consent. How do they correctly withdraw?

Answer 13

withdraw must be in writing and cannot be by word of mouth

Question 14

HIPPA

Answer 14

policy on who has access of patient records

Question 15

how do you get a certificate of confidentiality to be immune to court order of releasing patient information?

Answer 15

write a letter to NIH asking for certificate of confidentiality and the IRB will even ask you to get one if information is very sensitive.

Question 16

the review by IRB will be on?

Answer 16

annual, semiannual basis

Question 17

objective of phase I trial?

Answer 17

determine dose appropriate in phase II trials

Question 18

patient of phase I trial

Answer 18

pts are of advanced disease resistant to standard therapy: good functional status and they have all tumor types to test on

Question 19

phase I trial dose escalation

Answer 19

start at 1/10 LD50 in dogs and then increase dose every 3-6 patients using modified fibonacci progression

Question 20

grades of toxicity

Answer 20

0
1
2
3
4

Question 21

In pharmacokinetics of phase I trial, what does the area under the curve represent for measuring serum concentration within hours of drug dose?

Answer 21

area under the curve is how long drug is prevalent in blood serum and cancer exposed

Question 22

what is the purpose of studying pharmacokinetics in phase I trial?

Answer 22

to reach dose that is minimally toxic in phase I

Question 23

Phase II clinical trial

Answer 23

test efficacy of MTD (maximal tolerable dose) of a drug
does the drug work?
pick one tumor type respondent in phase I and may be efficacious for this drug in phase II
minimal prior therapy and good KPS
show agent active in favorable group before trying in more debilitated pretreated patients

Question 24

phase II clinical trial objective

Answer 24

determine if drug has anti-tumor activity - measure response rate.

Question 25

phase III clinical trials endpoints

Answer 25

survival and patient welfare, not tumor shrinkage

Question 26

response in phase II trial does not garuntee ?

Answer 26

prolonged survival

Question 27

phase III clinical trial determines?

Answer 27

if drug makes patient with cancer live longer

Question 28

who writes protocol?

Answer 28

experienced investigator at cancer center and company doctors

Question 29

protocol takes into account?

Answer 29

animal data and decides best regimen for progression, pharmacokinetics, and dynamics

Question 30

purpose of IRB is to?

Answer 30

protect vulnerable subjects

Question 31

Nurenberg code

Answer 31

crimes against humanity

Question 32

Helsinky declaration

Answer 32

conduct of clinical research

Question 33

ethical issues for phase I?

Answer 33

phase I - subject with incurable disease toxicity vs benefit study vs therapeutic intent - low chance of response, must not mislead patient wants to please doctor conflict of interest - publish, financial

Question 34

ethical issue for phase II?

Answer 34

still low probability of benefit of survival oncologist's biases less complex - looking for efficacy, less likelihood of unexpected toxicity

Question 35

phase III looks for ??

Answer 35

efficacy (length of survival) and not shrinkage of tumor

Question 36

phase III ethical issues

Answer 36

no true neutrality | permission to randomize patient- doctor gives up primary responsibility

Question 37

what is the only ethical way to answer important questions and forward progress of medical care?

Answer 37

conducting phase III study

Question 38

NIH toxicity criteria 0-4

Answer 38

0 - normal 1 - abnormal 2- no requirement of treatment or aid 3 - abnormality correctible with aid or treatment 4- severe abnormality, not correctable by aid or treatment

Question 39

subject headings for protocols

Answer 39

introduction of story objective pt selection study design treatment plan drug info toxicities monitored and dose modifications clinical and lab data and calendar criteria to evaluate treatment; defined endpoint stats; data forms informed consent, investigators, IRB chair, phone #s

Question 40

response evaluation criteria in solid tumors (RECIST)

Answer 40

measurable disease - at least 1 measurable lesion measurable lesions of cancer- lesion measured in at least 1 dimension with longest diameter non-measurable lesions of cancer- all other lesions with longest diameter

Question 41

what is the minimum KPS for clinical trial protocols?

Answer 41

70% or higher | 70% patient stays home and can take care of self

Question 42

karnofsky perfomance status (KPS)

Answer 42

``` 0% = death 50% = hospitalization 70% = stays home and minimum for protocols 100% = normal, no complaints, no signs of disease ```

Question 43

ECOG/Zubrod performance status

Answer 43

0 - asymptomatic 1 - symptomatic but ambulatory 2- sympotomatic, <50% in bed during the day and is minimum for protocols 3- symptomatic, >50% in bed, but not bedbound 4 - bedbound 5 - death