, start up meeting for stage 2. response rates in phase 3 trials chemotherapy response rates %...
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,START UP MEETING FOR STAGE 2
Response Rates in Phase 3 Trials
Chemotherapy Response rates %
Liposomal doxorubicin 10-12
Gemcitabine 5-9
Gemcitabine + Pertuzumab 13
Topotecan 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.
REGISTER
REGISTER
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 formsindependently
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 formsindependently
Stage1100 patients
• Complete 7 QoL forms• 20 subjects will participate in additional QoL telephone interview
Stage1100 patients
• Complete 7 QoL forms• 20 subjects will participate in additional QoL telephone interview
Data Collection
4 Treatment
cycles or
Disease progression
Data Collection
4 Treatment
cycles or
Disease progression
Study Schema
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 15
Symptom control + radiological evidence only 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 SYMPTOM
% Patients reported (N=83)
% AE reported by clinician
(N=92)BOTH TREATMENT & DISEASE
FATIGUE 40% 55%
PREDOMINANTLY DISEASE RELATED
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%)
PREDOMINANTLY EMOTIONAL
SLEEP DISTURBANCE 27% 4%
DEPRESSION/MOOD PROBLEMS 12% 5%
Number of Lines of Prior Therapy
Previous Lines
Patients89
1 222 263 204 75 66 27 1
UK 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
MOSTMeasure 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
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Data Collection
• Baseline
• Each treatment cycle
• One month post completion of treatment or until disease progression
Data Collection
• Baseline
• Each treatment cycle
• One month post completion of treatment or until disease progression
Target Population
•Informed consent
•≥18yrs
•Platinum Resistant/Refractory
•ECOG 0-3
•Life expectancy > 3 months
•Able to commence treatment within 2wks of registration
•Able to complete questionnaires independently
Target Population
•Informed consent
•≥18yrs
•Platinum Resistant/Refractory
•ECOG 0-3
•Life expectancy > 3 months
•Able to commence treatment within 2wks of registration
•Able to complete questionnaires independently
Stage 2
Primary Objective To determine: The criteria for defining a clinically significant subjective
improvement and the optimal instrument/s to measure benefitSecondary 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 participationCanada (additional sites) To be confirmedUnited Kingdom JapanIreland SpainGermany Scandinavia Italy FranceUSA- selected sites
Study Chair: Professor Michael Friedlander ANZGOG
Coordinating Centre: Symptom Benefit NHMRC Clinical Trials Centre
Locked Bag 77 CAMPERDOWN NSW 1450
AUSTRALIA
Study team: [email protected]
Central Coordinator: Kim Gillies +61 2 9562 [email protected]
Data Manager: Lisa Martyn +61 2 9562 5394 [email protected]
Program Manager: Julie Martyn +61 2 9562 [email protected]
Central Study Contacts