1. Clinical Trials Oct. 6, Lyon France
Birthe Lemley
Executive Board Member of ENGAGe
President of KIU – Danish Patient Organisation for
Women with Gynaecological Cancer
Board Member of EUPATI, Denmark

2. What is a Clinical Trial?
A clinical trial can be started by a pharmaceutical company or
by an investigator (typicalley a doctor/professor at a hospital or other institution)
If the trial is started by an investigator, there is often a collaboration with one or more pharmaceutical companies if drugs are involved in the clinical trial
Usually clinical trials are international (multiple sites) – meaning that hospitals from several countries are involved in the clinical trial
A clinical trial can be open or blinded. If it is blinded the patient does not know which drug she is taking (the drug being tested or a comparison drug/placebo) (the doctor can also be blinded).
A clinical trial is often randomised meaning that the patient is either participating in the arm with the new drug or in the arm with a comparison drug/placebo.
Randomisation is not always 1:1. It can also be 2:1 or another combination.

3. What is a Clinical Trial?
In randomised controlled trials, trial participants are randomly assigned to either treatment or control arms. The process of randomly assigning a trial participant to treatment or control arms is called ‘randomisation’. Different tools can be used to randomise (closed envelopes, computer generated sequences, random numbers).
The clinical trial must be approved by an ethics committe.
When a patient has accepted to participate in a trial, she is asked to sign an informed consent
The patient can withdraw from the trial at any time.

4. What is a Clinical Trial?
The 3 phases of a trial
Phase I – only a small number of patients are included.
Purpose: establishing safety and the dosage of the drug
Duration: several months
Phase II – Up to several hundred patients with the disease/condition.
Duration: several months to 2 years
Purpose: antitumor activity and side effects, also after multiple cycles in an “idealized” situation (patients are usually very similar)
Phase III – 300 to 3,000 people with the disease or condition
Duration: 1 to 4 years
Purpose: clinical advantages over standard treatment in daily life (efficacy and side effects)

5. Outline of the content of a study protocol
The study protocol
Outline of the content of a study protocol
Project summary/abstract
General information
Protocol title, protocol identifying number (if any), and date.
Name and address of the sponsor/funder etc.
Name and title of the investigator(s)
Name(s) and address(es) of the clinical laboratory(ies) and other medical and/or technical department(s) and/or institutions involved in the research
Rationale & background information
The Rationale specifies the reasons for conducting the research in light of current knowledge and examines benefits and harms of each intervention.
Roles and responsibilities

6. Development of a New Drug/New Treatment
Placebo
Substance or treatment with no active therapeutic effect. A placebo can be made to resemble an active medication or therapy so that it functions as a control.
Problems in study design with placebo
Placebo as control when there is a recognized standard treatment of proven efficacy.
No possibility of cross-over when the tumor doesn’t respond to the first therapy.
Treatment with placebo is burdensome for patients.

7. The Outcome of a clinical trial Niraparib – a parp inhibitor
How to read the results of a clinical trial:
Niraparib – a parp inhibitor
Example:
Parp inhibitor – Niraparib used for maintenance treatment of relapse in high grade serous ovarian cancer patients.
To evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer.
A randomised, placebo-controlled, phase 3 trial. Two independent cohorts on the basis of the presence or absence of germline BRCA mutation were enrolled. Patients were randomly assigned in a 2:1 ratio to receive niraparib or placebo.

8. Inclusion criteria: 18 years
Histologically diagnosed ovarian, fallopian tube or primary peritoneal cancer
High grade serous histology
Received at least 2 previous courses of platinum-containing therapy
Responded to last regime – platinum sensitive

9. Exclusion criteria:
Known hypersensitivity to the components of niraparib
Invasive cancer other than ovarian cancer within 2 years
Symptomatic uncontrolled brain metastases
Pregnant or breast feeding
Prior treatment with a known PARP inhibitor

10. Cohorts in the trial OS – Overall survival
PFS – progression-free survival was assessed independently as follows:
gBRCA cohort (patients with BRCA1/2 mutations – hereditary ovarian cancer)
Non-gBRCA cohort (non-hereditary BRCA mutations)
HRD positive (homologous recombination DNA deficiency)
HRD negative

11. Outcome of the Clinical Trial
Results of PFS for gBRCA cohort
PFS of 21 months versus 5.5 months for placebo – a difference of 15.5 months
(Hazard ratio: 0.27 – reduced the risk of disease progression or death by 73 %)
PFS for the non-gBRCA cohort
PFS og 9.3 months versus 3.9 months for placebo – a difference of 5.4 months
(Hazard ratio: 0.45 – reduced the risk of disease progression or death by 55 %)
P-value = low p-value = strong evidence e.g. p>0.0001

12. Other important issues in a clinical trial
Adverse events
Haematological AEs
Nausea
Vomiting
Constipation
Fatigue
Hypertension
Health related Quality-of-Life
Always measured according to various validated questionnaires

13. Why enter a clinical trial?
What could be the advantages for patients to participate in a clinical trial?
For you as a patient?
For other patients?
Has any of you every participated in a clinical trial. If yes, let us know why you decided to participate in a clinical trial?

14. Where do I find an overview of clinical trials?
Usually a local overview in each country