Symptom Benefit Working-group. General Assembly, May 29, 2015

Transcription

1 Symptom Benefit Working-group General Assembly, May 29, 2015

2 Agenda General Topic : Supportive care Working group session : how to integrate PROs in clinical trials To prepare the Tokyo Meeting Update of the SB studies

3 Best Supportive Care : Integration into Clinical Trials Lois Ramondetta MD Professor Gynecologic Oncology MD Anderson Cancer Center Houston Texas

4 Outline Goals of palliative chemotherapy Trial End points Defining the intervention Trial Design Recruitment Issues

5 Palliative Care Improves Outcomes QOL Higginson IJ Cancer J 2010; 16; Bakitas M JAMA 2009; 302: El-Jawahri A J Support Oncol 2011;9;87-94 Survival Temel JS N Engl J Med 2010; 363;

6 BSC in Clinical Trials Clinicaltrials.gov (>200 active trials with BSC arm) Testing of new targeted agents vs BSC None are in Gyn Tumors However-almost all lack definition Thus-lack of clinically useful information Over or underestimate value of new agent Cost often not included health care

7 Definition 7 Major Themes for Ambulatory PC Both visits included discussions about symptoms and illness status Oncologic visits focused on treatment and medical complications. PC visits emphasized symptoms and psychosocial elements (1)Relationship and rapport building (2)Addressing symptoms (3) Addressing coping (4) establishing illness understanding (5) discussing cancer treatments (6) end-of-life (EOL) planning (7) engaging family members Yoong Temel et al JAMA Intern Med

8 Consensus Definition-Evidence Based Supportive Care Highest scored components Symptom management Baseline & follow up assessment validated instruments Symptom assessment intervals same in groups Evidence based guidelines for symptom management (NCCN, ESMO) Documentation of supportive care interventions Access to palliative care specialists Communication of goals of care Zafar S Y AP Abernethy Lancet Vol

9 Outline Goals of palliative chemotherapy Trial End points Defining the intervention Trial Design Recruitment Issues

10 Two designs of best supportive care studies. Discussion of the group Nathan I. Cherny et al. JCO 2009;27: Ovarian cancer > 3 lines : New targeted therapy plus BSC versus BSC including Chemotherapy Ovarian cancer > 3 lines : Standard chemotherapy plus BSC by physicians (routine) versus Standard chemotherapy organized BSC according to recos 2009 by American Society of Clinical Oncology

11 Recurrent Cervical Cancer 1-2 prior systemic therapies R A N D O M I Z E Best Supportive care Best Supportive Care Plus 227 Queue enrollment OR Cytotoxic of choice Proposed to RTOG

12 Working group session Guidelines to integrate QoL in Ovarian clinical trials? Preparation of the 5th Ovarian cancer consensus conference Michael Friedlander and all

13 Guidelines for Incorporating Patient Reported Outcomes/QoL in GCIG Ovarian Cancer Trials There are many existing guidance documents that are fit for purpose The 5 th Ovarian Cancer Consensus Meeting Tokyo November 2015 japan-guide.com

14 what should we do? - Endorse a specific guidance document e.g CONSORT PRO - Agreeing on a Checklist/ Guidance document alone unlikely to change practice - As a group need to discuss and reach consensus regarding the most relevant/important context specific PRO endpoints - Aim to have consistency in reporting across trials in the same patient populations - Agree how to best present the results so they are clinically relevant and can be understood and help inform practice Endorsement of a PRO guidance doc e.g CONSORT PRO or SPIRIT-PRO PRO endpoints/outcomes that are clinically relevant, understandable and provide context and meaning

15 PRO Endpoints- context specific - First line- good prognosis late toxicities and survivorship - First line-poor prognosis- acute toxicities- symptom improvement- prolongation of time to symptomatic progression - Maintenance therapy- 1 st line good/poor prognosis -2 nd line treatment - Recurrent disease good prognosis vs. poor prognosissymptom benefit/ae s - Surgical trials - Prevention trials - Special populations e.g elderly

16 Ongoing studies

17 OvQuest, MOST-Opale, ECHO, Systematic review

18 Symptom Benefit Does palliative chemotherapy improve symptoms in women with recurrent ovarian cancer?

19 Trial Status ANZGOG-0701 TOTAL ACCRUAL ANZGOG ICORG AGO MITO CANADA GINECO NSGO UK JAPAN USA Closed to recruitment 31 December 2014

20 Current Analyses MOST Validation MOST- MCID ISOQOL ESGO Analysis of patient outcomes- general overview Prognostic Factors Prognostic Index HRQoL as a prognostic factor for outcome-?identifying patients who should not be treated Patient expectations and perceived benefit 2 posters at ASCO 2015

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24 MOST-OPAL Primary objectives: To (i) investigate the ability of the MOST questionnaire to detect symptoms of recurrence during follow up and To (ii) document the adverse-effects after completion of first line chemotherapy. Recrutment Months: MOSTs:

25 OvQuest : Self-reported questionnaire Eligibility: >18, diagnosed at least 6 months ago, received chemo Recruited in Australia USA, UK, Canada 1013 completed surveys 445 partial Ethics approval in Germany Australian data presented ANZGOG and IGCS 2015 International data submitted to ESGO 2015 Obesity, physical inactivity and symptoms after ovarian cancer treatment

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27 Expression IV What do primary and recurrent ovarian cancer (OC) patients expect from maintenance therapy? (ENGOT-ov22) Participating countries: Austria (A-AGO), Belgium (BGOG), Italy (MITO), Finnland (NSGO), Romania, Slovenia, France (GINECO), Turkey, Germany (NOGGO)

28 number of participants participants online paper Country status: : ~ 1000 pts Interims analysis of 641 patients from 6 countries Submitted to ESGO 2015 in Nice

29 AGO OVAR 19 TRIAL ON RADICAL UPFRONT SURGERY IN ADVANCED OVARIAN CANCER INCLUDING EVALUATION OF FRAGILITY AND LONG TERM QUALITY OF LIFE

30 AGO OVAR 19 - QoL longitudinal with specific topics for TRUST all Pts with suspicion for OC III- IV FRAGILE: prim. Endpoint: 10-PFS F R A G I L E S c r e e n i n g Allocation to study/ Randomisation/Strat ification QoL every 3 months until first recurrence/progression Z1 Z2 Z3 Z4 Z5 Z6 EoT QoL every 3 months until first recurrence/progression PDS Z1 Z2 Z3 Z4 Z5 Z6 EoT QoL every 3 months until first recurrence/progression QoL TRUST Z1 Z2 Z3 Z4 Z5 Z6 EoT IDS every 3 months until first recurrence/progression Best Supportive Care QoL-BL 1. ROC QoL-BL 1. ROC QoL-BL 1. ROC every 3 months until first recurrence/progression every 3 months until frecurrence/progression every 3 months until frecurrence/progression QoL-BL 2. ROC QoL-BL 2. ROC QoL-BL 2. ROC QoL-BL every 3 months until recurrence/progression 3. ROC every 3 months until recurrence/progression every 3 months until recurrence/progression QoL-BL 3. ROC QoL-BL 3. ROC

31 Identifying pts without benefit from standard OP CTX AGO OVAR 19/FRAGILE All pts. with suspected AOC PROSPECTIVE SURVEY OF VARIABLES Charlson-Comorbidity-Index HADS-Score time up and go test Symptoms: y/n abdominal bloating y/n abdominal pain j/n dyspnea j/n Lab-values: Albumine, S-Kreatinin Hemoglobin, Leukocytes, Thrombocytes CA 125 ASA and ECOG Suspected FIGO IV y/n Estimated ascites volume Palliative paracentesis prior OP y/n weight/height/bmi Therapy according to physicians choice (TRUST optional, NACT optional) Documentation of: Surgical complexity and outcome, FIGO-Stage, histology, complications, revision-op, CTX, cycles, post-t ECOG Follow-Up for 10 months after Registration Primary endpoint: identification of fragile pts without benefit from standard OP CTX (=progression/death within 10 months) Secondary endpoint: 3 months survival, feasibility (time to 1st cycle, cycles, residual tumor, FIGO-Stage, ECOG after 6 months, 6 months PFS, revision surgery)

32 PRO endpoints in AGO OVAR 19 Start: Q Recruitment: N=440 patients within 15 months. Instruments: EORTC QLQ-C30 and QLQ-OV28 Time points: at baseline and then every 3 months (+/- 30 days) until month 36 In patients without progression 18 months after end of chemotherapy (not maintenance) the interval is extended to 6 months. In case of a new progression an additional QoL assessment have to be performed within 30 days and repeated in pre- defined 3 months intervals calculated from registration. For all patients (surgical and extended part) Co-Primary: Long term Quality of Life (QoL) to describe the influence of treatment and course of disease on quality of life For TRUST-Pts. Primary: General Helath status 24 months after randomization (PDS vs NACT)

33 Paola QOL Substudy

34 Patient Reported Outcome (PRO), Quality of Life (QoL) and Pharmacoeconomics in PAOLA-1:

35 Patient Reported Outcome (PRO): Important Issues to be Considered International Commitment for PAOLA Participation of GCIG Symptom Benefit Working Group an international QoL Committee will be put in place for the SAP Validated tools for PRO and QoL in PAOLA QLC30 + OV28 EQ-5D Utility Index

36 When to deliver questionnaires? at baseline, 12 weeks during 2 years, even after disease progression +++ Sub study with App for mobile device (smartphone or tablet) :feasibility of every week collection

37 Additional secondary objectives : Elderly GVS Introducing the notion of fragility in 1 st line trial > 70 years old GVS screening score ADL < 6 score IADL < 25 score HADS > 14 albuminemia < 35g/L lymphopenie < 1G/L Vulnerable patient if GVS > 3

38 Exploratory analysis : Pharmaco-economics Assessment of costs Hospitalization form in the e-crf Hospitalization form Date of hospitalization - Type of hospitalization: medical, surgery, obstetric ward - Type and reasons for hospitalization - If inpatient hospitalization, reason - Rehabilitation and follow-up care -Transfusions

39 Survivors

40 6/30/2015 Living after epithelial ovarian cancer Assessment of quality of life and health needs in long-term Epithelial Ovarian Cancer Survivors French GINECO Study 43

41 6/30/2015 Inclusions criteria Epithelial ovarian cancer No relapse at least since 3 years from the end of the chemotherapy One previous line of treatment Maintenance anti-angiogenic treatment permitted 44

42 6/30/2015 Design Multicenter study (Two parts): Part 1 : Case-control study (215 pts and 215 controls planned) To compare QOL, Fatigue, Psycho-social difficulties to population based controls Part 2 : Group of patients : Characteristics of long term survivors and specific needs and sequelae (120 pts planned) Evaluation of gynaecological sequelae Evaluation of specific needs Evaluation of biological parameters 45

43 6/30/2015 Recrutement Start of inclusions : December 2014 Part 1 : Case-control study 26 French Centers, 129 patients Part 2 : Group of patients : Characteristics of long term survivors (clinical, needs and biology) 18 French Centers, 16 patients 47

44 The Long-term Ovarian Cancer Survivor Project (long-term (10 years) survivors ) A Department of Defense Initiative PI: Michael Birrer Co-PI: Lari Wenzel GOG Chair: Philip DiSaia Advocates Chair: Mary Scroggins DODLT Project

45 Overall Grant Structure Phase I Two years grant Awarded to three teams Build consortium Establish function network Demonstrate effective communication Engage advocates Phase II 5 year grant One award Use consortium to obtain definitive data Written and oral presentation for application Obtain initial data

46 Specific Aims To determine the genetic and immunologic features of Long Term versus Short Term survivors To validate a genetic signature that predicts for recurrence of early-stage, high-grade EOC To determine the extent to which health-related QOL measures, additional PROs, and key CTCAE criteria predict LT OC survival. To examine, as an exploratory aim, the potential relationship between health-related QOL, PROs, and key CTCAE criteria and genomic features predicting disease recurrence.

47 Current Work Flow MGH and UCI Bi-monthly calls with GOG Monthly calls with AAB Non-GOG patient recruitment and engagement Develop QOL collection and analysis tools Coordinate tissues molecular analysis with research sites GOG Identifies potentially available tissues and data Develops protocols for collection and distribution of material Biostatistical analysis of QOL Collects and processes tissues for distribution Leadership Michael Birrer, PI Lari Wenzel, Co-PI Mary Jackson, AAB Chair Advocates Advisory board AAB Advertizes and educates the patient community for this project Identifies non-gog patients to be recruited Supports development of consent forms and other IRB material

48 What We Need from You to Enter Phase II: 1) Written support: collaboration letter for Phase II 2) Estimate of material available (QOL data, tumors, trials etc) 3) Engagement of advocates 4) Plan for regulatory requirements

49 EmQuest Life after the diagnosis and treatment of endometrial cancer A survey of symptoms and concerns in women who have been treated for endometrial cancer K Webber, J McAlpine, M Friedlander, L Mileshkin

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