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R
System. Lymphadenectomy
pelvic
para-aortic
no Lymphadenectomy
epithelial invasive ovarian cancer
FIGO IIB - IV
ECOG 0/1 and no CI against LNE
no visible extra- and intra-abdominal
tumor residuals
no bulky lymph nodes
Endpoints: OS, PFS, QoL Strata: centre, PS ,age
Lymphadenectomy In Ovarian Neoplasms
AGO – OVAR OP.3 (LION)
80/ 640
Supported by Deutsche Forschungsgemeinschaft
Carbo Paclitaxel +/- BIBF 1120 (Vargatef)
Patients 0 / 1300 (2:1 random)
Leading AGO-OVAR
Participating AGO Austria, BGOG, GINECO,
MANGO, MITO, NSGO, US Oncology
AGO-OVAR-12
Multicenter, randomised, double-blind, Phase III trial to investigate the efficacy and safety of Vargatef (BIBF 1120) in combination with standard
treatment of carboplatin and paclitaxel compared to placebo plus carboplatin and paclitaxel patients with advanced ovarian cancer
AGO-OVAR12
R
CT
CT
CT
CT
CT
CT
CT
CT
CT
CT
CT
CT
= Vargatef 2 x 200 mg po qd
= Placebo
120 weeks
C = Carboplatin AUC 5-6 d1
T = Paclitaxel 175 mg/m2 (3h) d1
q21d / 6 courses
Vargatef / Placebo :- no intake on days of chemotherapy
- dose: 200 mg po bid (combi + mono)- dose adaptation in case of undue toxicity
- max. duration of 120 weeks in non-progressing pts
SURGERY
n=1300
Pazopanib consolidation 1 yrFirst Line Chemotherapy
Control
Patients 80 / 900
Leading AGO-OVAR
Participating AGO Austria, ANZGOG, BGOG, GEICO, GINECO, ICORG, JGOG, KGOG, MANGO, MITO, NSGO, US-Sites: California Consortium, NY GOG, SWOG
AGO-OVAR 16
AGO-OVAR16A Phase III Study to Evaluate the Efficacy and Safety of Pazopanib Monotherapy Versus Placebo in Women Who Have not Progressed after First Line Chemotherapy for Epithelial Ovarian, Fallopian Tube,
or Primary Peritoneal Cancer
Survival Follow-up(post-PD)
First-line Chemotherapy
(allow ip, neoadj) Placebo
(12 months)
Pazopanib (12 months)
If not PD
Treatment PeriodR
ANDOMIZE
Observation (to PD)
ScreeningBaseline
Post-Treatment Period
Follow-up Period
Carbo Topo vs Chemo (CT or CG) in recurrent Platinum-sensitive ovarian cancer
Patients 508 / 550
Leading NOGGO/AGO-OVAR
Participating AGO-AUSTRIA, GEICO
HECTOR
CT vs CDDP + Irinotecan
Patients 416 / 652
Leading JGOG
Participating GINECO, GOG, KGOG, MITO, SGCTG
JGOG-3017 Clear Cell Carcinoma
JGOG3017/GCIGOvarian Trial Protocols
Randomized Phase III Trial of Paclitaxel plus Carboplatin (TC) Therapy versus Irinotecan plus
Cisplatin (CPT-P) Therapy as a First Line Chemotherapy for Clear Cell Carcinoma of the Ovary
Study Chair Toru Sugiyama, MD (Iwate Medical University)Study Co-Chair Seiji Isonishi, MD (Jikei University School of Medicine)
Fumitoshi Terauchi, MD (Toho University)
RA
ND
OM
IZA
TIO
NTC
Paclitaxel 175 mg/m2 (d1) Carboplatin AUC 6 (d1)
Every 3 wk x 6
CPT-11/CDDP CPT-11 60 mg/m2 (d1, 8, 15)
Cisplatin 60 mg/m2 (d1)Every 4 wk x 6
International Cooperative Phase III Study for Clear Cell Carcinoma
-Clear Cell Ca
-Stage I~IV
225 patients in each arm, 450 total for 3 years
326 patients in each arm, 652 total for 4.25 years
JGOG3017/GCIG TRIAL
Weekly CT vs 3-weekly CT (QoL)
Patients 72 / 500
Leading MITO
Participating MaNGO, AGO-OVAR
MITO-7
Trial design
• Aim of the trial is to compare the quality of life of weekly somministration of carboplatin plus carboplatin (experimental arm) versus every 3 weeks administration of the same drugs (standard arm) in 1°-line advanced ovarian, tubal and peritoneal cancer
RANDOM
Carboplatin AUC 2Paclitaxel 60 mg/mq
day 1,8 15 - every 21days
Carboplatin AUC 6Paclitaxel 175 mg/mq
day 1 - every 21days
PLD vs CT cross-overin 6-12 m platinum-free interval
Patients 18 / 253
Leading MITO
Participating MaNGO, AGO-OVAR, Belgium
MITO-8
RANDOM
LIPOSOMALDOXORUBICIN
40 mg/mqday1 every 28 days
CARBOPLATIN AUC 5 +PACLITAXEL 175 mg/mq
day1 every 21 days
Cross-over atProgression
CARBOPLATIN AUC 5 +PACLITAXEL 175 mg/mq
day1 every21gg
LIPOSOMALDOXORUBICIN 40 mg/mq
day1 every 28 days
Trial design• The objective of this trial is the efficacy determined
through analysis of overall survival (OS) of the different sequence (CP→PLD vs PLD→CP) in recurrent ovarian cancer patients with platinum-free interval 6-12 months
ICON6: A randomised trial of concurrent (with platinum based chemotherapy) and maintenance
cediranib (AZD2171, Recentin) in women with platinum-sensitive relapsed ovarian cancer.
Gynaecologic Cancer Intergroup TrialStage 1 MRC/NCRI, NCIC
Stage 2 ANZ-GOG, IMN, EORTC, GINECO, GEICO, MANGO, NSGO, ICMB and others
ICON 6 Start up slidesOct 2009
ICON 6 Design schema
Arm AReference arm
6 cycles of chemotherapy
plusPlacebo
No Progressive disease
Maintenancecediranib after chemotherapy
Maximum 18 months from
randomisation
Arm BChemotherapy
Pluscediranib
during Chemotherapy
Arm CChemotherapy
pluscediranib
during Chemotherapy
No Progressive diseasePlacebo
Maximum 18 months from
randomisation
No Progressive diseasePlacebo
Maximum 18 months
from randomisation
2:3:3 RANDOMISATION
ICON6 Cediranib Dose Reduction
• Cediranib dose initially selected at 30mg/d in ICON6. Reduced to 20 mg
• Stage I re-started• Stage I now completed 103 patients
entered (11 UK; 6 CDN)• Stage II being prepared with expansion
of chemotherapy options to be discussed by ITMG Sunday 11th Oct- Belgrade
ICON 6 Start up slidesOct 2009
Planned TrialsPlanned Trials
Cytoreductive surgery vs NO surgery in platinum-sensitive recurrent EOC
Patients 0 / 385
Leading AGO-OVAR
Participating ?
AGO-OVAR-OP.4 DESKTOP III
AGO-OVAR-OP.2 DESKTOP II
Study collective: AGO score + 1st relapse129 pts (87%)
08/06 – 03/08: Screening of 516 pts with platinum-sensitive relapse in 46 centres
Score positive+
First relapse
Frequency of complete resection by applying the AGO Score
76%Completeresection
AGO-OVAR DESKTOP III (Protocol AGO - OVAR OP.4)
A randomized trial evaluating cytoreductive surgery in patients with platinum-sensitive recurrent ovarian cancer
Complete resection
seems feasible and a
positive AGO-score
Strata:
Platinum-free-interval
6-12 vs > 12 months
- 1st line platinum
based chx: yes vs no
RANDOM
Cytoreductivesurgery platinu
m-based
chemo-therapy
*recommende
d
no surgery
The next steps:
Protocol finalized (-> review participating groups)
Ethical approval for Germany:12/09 -> FPI 01/2010
Identifikation of interested GCIG-groups/single centres
-> representatives contact:
Again limited funding - participating groups have to pay local costs
(DESKTOP II model – Presentation/Publication/Co-authorship)
AGO-OVAR DESKTOP III (Protocol AGO - OVAR OP.4)
Collaborative Nursing Study MITO12Pathway to diagnosis of ovarian cancer in Italian
women: an exploratory study
Primary Objectives• Describe the frequency and duration of symptoms in
the 12 months preceding the diagnosis of ovarian cancer (Goff symptoms survey)
• Describe time intervals of sentinel events– Onset of persistent symptoms– First physician visit– Diagnosis of ovarian cancer
• Describe the pathway to diagnosis according to Andersen’s model of “total patient delay”
Weekly Paclitaxel vs weekly Paclitaxel and Pazopanib in patients with
resistant/refractoryovarian cancer:
Phase II randomized multicenter trial
MITO - 11
Trial design
• Aim of the trial is to compare the PFS of weekly paclitaxel vs weekly paclitaxel and pazopanib
RANDOM
Pazopanib 800 mg/dayPaclitaxel 80 mg/mq
day 1,8 15 - every 28days
Paclitaxel 80 mg/mq
day 1, 8, 15 - every 28 days
IP vs IV carboplatin + weekly Paclitaxel
Patients
Leading JGOG
Participating
JGOG IP Trial
iPocc Trial DesignEpithelial Ovarian, Peritoneal,
Fallopian Tube CancerStages II-IV
Optimal, SuboptimalExcluding Clear Cell Carcinoma
Paclitaxel 80 mg/m2 IV WeeklyCarboplatin AUC 6 IV
Q21, 6-8 Cycles
Paclitaxel 80 mg/m2 IV WeeklyCarboplatin AUC 6 IP
Q21, 6-8 Cycles
Randomization
Primary Endpoint: PFSSecondary Endpoint: OS, Toxicity, QOL, Cost
oxaliplatin + capecitabine ± bevacizumab vs carboplatin + paclitaxel ± bevacizumab Patients 0/332
Leading NCRI/SGCTG GOG
Participating AGO OVAR, GINECO, MaNGO, NSGO, KGOG
MucinousEOC
Cancer Research UK & UCL Cancer Trials Centre
Targets: Planned start date – November 2009; Planned end date – May 2014
European Sites: Interest from sites in
UK, Denmark, Finland, Sweden, Norway, France, Italy & Germany.
Approximately 40 UK sites interested. Trial is in set-up, no centres are open.
Chief Investigator: Prof. Martin Gore
Sponsor: University College London
http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=4667
Contact Email: [email protected]
TC dose dense / 3weekly ± BEVACIZUMAB
Patients 0 / 2000
Leading MRC/NCRI
Participating ?
ICON-8
Randomisation
ARM1: C q 3/52 P q 3/52(current std)
ARM2: C q 3/52 P q 1/52
ARM3: C q 1/52 P q 1/52
Current Proposal
(A) Immediate Primary Surgery (IPS)
(B) Delayed Primary Surgery (DPS)
Surgery (IPS)
Surgery (DPS)
Chemotherapy(ARM 1-3 x 6)
Chemotherapy(Arm 1-3 x 3)
Chemotherapy (Arm 1-3 x 3)
One trial with pre-specified
stratification for IPD v DPS
Plan to use lower dose of paclitaxel than JOG for arm 2: Carboplatin AUC6 d1Paclitaxel 60mg/m2 d 1,8,15 q3w
JOG study 60% received 6 cycles, 48% required at least one dose reduction and 76% had at least one delay, doses used carboplatin AUC6 and paclitaxel 80 mg/m2
IP/IV Platinum/T vs IV CT optimally debulked following NACT
Patients 0 / 780
Leading NCIC CTG
Participating GEICO, NCRI, SWOG
NCIC CTG OV.21
Basic Design
Patients with EOC
3-4 cycles neoadjuvant chemo
Initial surgery: < 1 cm residual
3 cycles IV Carbo/Taxol
3 cycles IP/IV platinum and taxol
Endpoints: PFS and OS
RR
Day 8th Day 8th
Optimal Optimal SurgerySurgery
ShorteShorter r
coursecourse
Phase IIPatients will be randomized to one of the following three arms:
Arm Agent(s) Dose Route DurationSchedule
Days Repeat
1
Paclitaxel135 mg/m2
IV
3 hours Day 1
Every 21 days
60 mg/m2 1 hour Day 8
Carboplatin
AUC 5if measured GFR
(use AUC 6 if calculated GFR)
30 minutes*
Day 1
2
Paclitaxel
135 mg/m2 IV 3 hours Day 1
60 mg/m2 IPBy gravity as rapidly
as possibleDay 8
Cisplatin 75 mg/m2 IPBy gravity as rapidly
as possibleDay 1
3
Paclitaxel
135 mg/m2 IV 3 hours Day 1
60 mg/m2 IPBy gravity as rapidly
as possibleDay 8
Carboplatin
AUC 5if measured GFR
(use AUC 6 if calculated GFR)
IPBy gravity as rapidly
as possible
Day 1
* or according to local practice
Phase IIIPatients will be randomized to one of the following two arms:
Arm Agent(s) Dose Route Duration
Schedule
Days Repeat
1
Paclitaxel135 mg/m2
IV
3 hours Day 1
Every21 days
60 mg/m2 1 hour Day 8
Carboplatin
AUC 5if measured GFR
(use AUC 6 if calculated GFR)30 minutes* Day 1
2 The selected IP arm from Phase II (regimen as in above table)
Every21 days
* or according to local practice
A randomised phase III trial of weekly carboplatin and paclitaxel versus pegylated liposomal doxorubicin in recurrent, platinum resistant, epithelial ovarian cancer
Patients 0 / 250
Leading SGCTG
Participating ?
DDPC-PREOC
Trial Design
Carboplatin (AUC 3) and paclitaxel (80 mg/m2) for 3 weeks out of 4 for 6 cycles
Pegylated Liposomal Doxorubicin (40 mg/m2) every 4 weeks for 6 cycles
RANDOMISE
250 patients with platinum resistant disease
Primary Endpoint: PFS
Secondary Endpoints: Overall SurvivalQuality of Life Health Economic AnalysisResponse RateToxicity/HypersensitivityDose Intensity Post progression therapy
Thank you for attention