,START
UP MEETING FOR STAGE 2
Response Rates in Phase 3 Trials
Chemotherapy
Liposomal doxorubicin
Gemcitabine
Gemcitabine + Pertuzumab
Topotecan
Response rates %
10-12
5-9
13
6
Trabectedin
7
Patupilone
15
Patients with good PS entered into clinical trials- 2nd Line Therapy
Symptom Benefit Study
Expectation is that Symptom Benefit > Response Rate
( otherwise why would we treat so many patients )
• How to best measure the impact of chemotherapy on
symptom improvement ?
• Can we use Symptom Benefit Measures as an
alternative outcome measure
• Can we identify patients most likely to benefit from
palliative chemotherapy?
Stage 1-Primary Aim
• The symptoms and aspects of HRQL
that are rated as most severe,
troublesome and important by
patients.
• The optimal items and
questionnaire/s for measuring these
improvements.
Study Schema
Target Population
• >18yrs
•platinum resistant/
refractory epithelial
ovarian cancer
/> 3 lines of therapy
•ECOG 0-3
•Able to commence
treatment within 2wks of
registration
•Sufficient English to
complete QoL forms
independently
R
E
G
I
S
T
E
R
Stage1
100 patients
• Complete 7 QoL
forms
• 20 subjects will
participate in
additional QoL
telephone interview
Data
Collection
4 Treatment
cycles
or
Disease
progression
Stage 1 QoL Questionnaires
•
•
•
•
•
•
•
•
Symptom Representation Questionnaire
FACT-O (includes FOSI)
EORTC QLQ-C30
EORTC QLQ-OV28
Patient Data Form
Expected and Perceived Benefit Scale
HAD Scale (Baseline & End of Treatment)
Herth Hope Index (Baseline & End of
Treatment only)
Results
• Majority Platinum Resistant
• Compliance 96%
All questionnaires were completed to
a very high compliance rate with few
or no missing data
Reasons for Starting Chemotherapy
REASONS FOR CHEMOTHERAPY
Patients
(N=89)
Symptom control only
1
Rising CA125 only
1
Radiological evidence only
1
Symptom control + rising CA125 only
Symptom control + radiological evidence only
15
4
Rising CA125 + radiological evidence only
19
Symptom control + rising CA125 + radiological
evidence
48
Patients “3 most noticed symptoms” and
clinician rated AE’s at baseline
CAUSE
BOTH TREATMENT &
DISEASE
PREDOMINANTLY
DISEASE RELATED
PREDOMINANTLY
EMOTIONAL
% Patients
reported
(N=83)
% AE reported
by clinician
(N=92)
FATIGUE
40%
55%
PAIN (ABDOMINAL/ UNSPECIFIED)
40%
32%
ABDOMINAL PROB/BLOATING
30%
17%
NAUSEA/VOMITING
20%
33%
BOWEL PROBLEMS
20%
27%
SHORTNESS OF BREATH
12%
2%
APPETITE LOSS
11%
(Anorexia 22%)
SLEEP DISTURBANCE
27%
4%
DEPRESSION/MOOD PROBLEMS
12%
5%
SYMPTOM
Number of Lines of Prior Therapy
Previous
Lines
1
2
3
4
5
6
7
UK
Patients
89
22
26
20
7
6
2
1
5
Improvement in quality of
life (Prior to Cycle 3 N=72)
Is your symptom improvement enough to affect your overall
quality of life?
Stage 1-outcome
Results have led to development of
MOST
(Measure of Ovarian cancer Symptoms and Treatment concerns)
Modification of Patient Data Form
COVERS ALL SYMPTOMS AND ASPECTS OF QOL
IDENTIFIED IN STAGE 1
MOST
Measure of Ovarian cancer Symptoms and Treatment
concerns
Comprises of 35 individual items on a discrete scale of 0-10, where
major symptomatic distress is represented by 10.
The first 15 items refer to disease symptoms
Items 16 and 17 refer to physical and emotional well-being
Item 18 is a question referring to overall well-being
Items 19-35 deals with side effects and other concerns
The study will examine the extent of clinical improvement by examining
changes in these items from baseline at each time point- to determine
MCID
Schema – Stage 2
Target Population
•Informed consent
R
•≥18yrs
E
•Platinum
Resistant/Refractory
•ECOG 0-3
•Life expectancy > 3 months
•Able to commence treatment
within 2wks of registration
•Able to complete
questionnaires
independently
G
I
S
T
E
R
Data Collection
• Baseline
• Each treatment cycle
• One month post
completion of treatment or
until disease progression
Stage 2
Primary Objective To determine:
The criteria for defining a clinically significant subjective
improvement and the optimal instrument/s to measure benefit
Secondary Objectives
• The proportion of women benefiting from palliative chemotherapy
• The time to symptom deterioration
• The proportion of women who receive treatment because they are (a)
symptomatic, (b) have rising tumor markers alone, or (c) have
imaging evidence of disease progression
• The percentage of patients who complete 4 or more cycles of
treatment
• The most common, most severe and most noticed symptoms as
perceived by patients.
• Develop a prognostic index
Stage 2
• MOST
• FACT-O
• EORTC QLQ C30
• EORTC OV28
• Expected and Perceived Benefits
These forms will be completed at Baseline and
after each cycle until chemotherapy ceases.
Prognostic Factors
Recruitment
The recruitment target is 600 evaluable patients
(~780 enrolled patients)
The estimated recruitment period is until December 2011
Currently there are 20 sites activated and 101 patients
recruited with a further 40+ sites to open
International participation
Canada (additional sites)
To be confirmed
United Kingdom
Japan
Ireland
Spain
Germany
Scandinavia
Italy
France
USA- selected sites
Central Study Contacts
Study Chair:
Professor Michael Friedlander ANZGOG
Coordinating Centre:
Study team:
Symptom Benefit
NHMRC Clinical Trials Centre
Locked Bag 77
CAMPERDOWN NSW 1450
AUSTRALIA
symptombenefit@ctc.usyd.edu.au
Central Coordinator:
Kim Gillies
+61 2 9562 5032
kim.gillies@ctc.usyd.edu.au
Data Manager:
Lisa Martyn +61 2 9562 5394
lisa.martyn@ctc.usyd.edu.au
Program Manager:
Julie Martyn +61 2 9562 5092
julie.martyn@ctc.usyd.edu.au