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AGO – OVAR OP.3 (LION)
Lymphadenectomy In Ovarian Neoplasms
epithelial invasive
ovarian cancer
System. Lymphadenectomy
 pelvic
FIGO IIB - IV
ECOG 0/1 and
no CI against LNE
no visible extraand intra-abdominal
tumor residuals
 para-aortic
R
80/ 640
no Lymphadenectomy
no bulky lymph nodes
Endpoints: OS, PFS, QoL
Strata: centre, PS ,age
Supported by Deutsche Forschungsgemeinschaft
AGO-OVAR-12
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-OVAR12
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
S
U
R
G
E
R
Y
R
C
C
C
C
C
C
T
T
T
T
T
T
= Vargatef 2 x 200 mg po qd
C
= Carboplatin AUC 5-6
d1
T
= Paclitaxel 175 mg/m2 (3h)
d1
q21d / 6 courses
n=1300
C
C
C
C
C
C
T
T
T
T
T
T
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
= Placebo
 120 weeks
AGO-OVAR 16
Pazopanib consolidation 1 yr
First 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-OVAR16
A 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
Screening
Baseline
First-line
Chemotherapy
(allow ip, neoadj)
If not PD
R
A
N
D
O
M
I
Z
E
Treatment
Period
Pazopanib
(12 months)
Placebo
(12 months)
Post-Treatment
Period
Follow-up
Period
Observation
(to PD)
Survival
Follow-up
(post-PD)
HECTOR
Carbo Topo vs Chemo (CT or CG) in recurrent
Platinum-sensitive ovarian cancer
Patients
508 / 550
Leading
NOGGO/AGO-OVAR
Participating
AGO-AUSTRIA, GEICO
JGOG-3017 Clear Cell Carcinoma
CT
vs
CDDP + Irinotecan
Patients
416 / 652
Leading
JGOG
Participating
GINECO, GOG, KGOG,
MITO, SGCTG
JGOG3017/GCIG
Ovarian 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
Study Co-Chair
Toru Sugiyama, MD (Iwate Medical University)
Seiji Isonishi, MD (Jikei University School of Medicine)
Fumitoshi Terauchi, MD (Toho University)
-Clear Cell Ca
-Stage I~IV
RANDOMIZATION
International Cooperative Phase III
Study for Clear Cell Carcinoma
TC
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
225 patients in each arm, 450 total for 3 years
326 patients in each arm, 652 total for 4.25 years
JGOG3017/GCIG TRIAL
MITO-7
Weekly CT vs 3-weekly CT (QoL)
Patients
72 / 500
Leading
MITO
Participating
MaNGO, AGO-OVAR
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
Carboplatin AUC 6
Paclitaxel 175 mg/mq
RANDOM
day 1 - every 21days
Carboplatin AUC 2
Paclitaxel 60 mg/mq
day 1,8 15 - every 21days
MITO-8
PLD vs CT cross-over
in 6-12 m platinum-free interval
Patients
18 / 253
Leading
MITO
Participating
MaNGO, AGO-OVAR, Belgium
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
RANDOM
LIPOSOMAL
DOXORUBICIN 40 mg/mq
CARBOPLATIN AUC 5 +
PACLITAXEL 175 mg/mq
day1 every 28 days
day1 every21gg
Cross-over at
Progression
LIPOSOMAL
DOXORUBICIN
40 mg/mq
day1 every 28 days
CARBOPLATIN AUC 5 +
PACLITAXEL 175 mg/mq
day1 every 21 days
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 Trial
Stage 1 MRC/NCRI, NCIC
Stage 2 ANZ-GOG, IMN, EORTC, GINECO, GEICO, MANGO,
NSGO, ICMB and others
ICON 6 Design schema
2:3:3 RANDOMISATION
Arm A
Reference arm
6 cycles of
chemotherapy
plus
Placebo
No Progressive
disease
Placebo
Maximum 18
months
from randomisation
Arm B
Chemotherapy
Plus
cediranib
during
Chemotherapy
No Progressive
disease
Placebo
Maximum 18
months from
randomisation
Arm C
Chemotherapy
plus
cediranib
during
Chemotherapy
No Progressive
disease
Maintenance
cediranib after
chemotherapy
Maximum 18
months from
randomisation
ICON 6 Start up slides
Oct 2009
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 slides
Oct 2009
Planned Trials
AGO-OVAR-OP.4 DESKTOP III
Cytoreductive surgery vs NO surgery
in platinum-sensitive recurrent EOC
Patients
0 / 385
Leading
AGO-OVAR
Participating
?
AGO-OVAR-OP.2 DESKTOP II
08/06 – 03/08: Screening of 516 pts with
platinum-sensitive relapse in 46 centres
Study collective: AGO score + 1st relapse
129 pts (87%)
Score positive
+
First relapse
76%
Complete
resection
Frequency of complete resection by
applying the AGO Score
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
R
A
N
D
O
M
Cytoreductive
surgery
no surgery
platinu
mbased
chemotherapy
*
recom
mende
AGO-OVAR DESKTOP III (Protocol AGO - OVAR OP.4)
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:
[email protected]
[email protected]
Again limited funding - participating groups have to pay local costs
(DESKTOP II model – Presentation/Publication/Co-authorship)
Collaborative Nursing Study MITO12
Pathway 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
Paclitaxel 80 mg/mq
RANDOM
day 1, 8, 15 - every 28 days
Pazopanib 800 mg/day
Paclitaxel 80 mg/mq
day 1,8 15 - every 28days
JGOG IP Trial
IP vs IV carboplatin + weekly Paclitaxel
Patients
Leading
Participating
JGOG
iPocc Trial Design
Epithelial Ovarian, Peritoneal,
Fallopian Tube Cancer
Stages II-IV
Optimal, Suboptimal
Excluding Clear Cell Carcinoma
Randomization
Paclitaxel 80 mg/m2 IV Weekly
Carboplatin AUC 6 IV
Q21, 6-8 Cycles
Paclitaxel 80 mg/m2 IV Weekly
Carboplatin AUC 6 IP
Q21, 6-8 Cycles
Primary Endpoint: PFS
Secondary Endpoint: OS, Toxicity, QOL, Co
MucinousEOC
oxaliplatin + capecitabine ± bevacizumab
vs carboplatin + paclitaxel ± bevacizumab
Patients
0/332
Leading
NCRI/SGCTG GOG
Participating
AGO OVAR, GINECO, MaNGO,
NSGO, KGOG
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]
Cancer Research UK & UCL Cancer Trials Centre
ICON-8
TC dose dense / 3weekly ± BEVACIZUMAB
Patients
0 / 2000
Leading
MRC/NCRI
Participating
?
Current Proposal
ARM1: C q 3/52
P q 3/52
(current std)
(A) Immediate Primary Surgery
(IPS)
Surgery
(IPS)
Randomisation
Chemotherapy
(ARM 1-3 x 6)
ARM2: C q 3/52
P q 1/52
(B) Delayed Primary Surgery
(DPS)
ARM3: C q 1/52
P q 1/52
Chemotherapy
(Arm 1-3 x 3)
Surgery
(DPS)
One trial with
pre-specified
stratification for
IPD v DPS
Chemotherapy
(Arm 1-3 x 3)
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
NCIC CTG OV.21
IP/IV Platinum/T vs IV CT
optimally debulked following NACT
Patients
0 / 780
Leading
NCIC CTG
Participating
GEICO, NCRI, SWOG
Basic Design
Patients with EOC
3-4 cycles neoadjuvant chemo
R
Initial surgery: < 1 cm residual
3 cycles
IV Carbo/Taxol
3 cycles IP/IV
platinum and taxol
Day 8th
Day 8th
Endpoints: PFS and OS
Optimal
Surgery
Shorter
course
Phase II
Patients will be randomized to one of the following three arms:
Schedule
Arm
Agent(s)
Dose
Paclitaxel
1
Carboplatin
Days
135 mg/m2
3 hours
Day 1
60 mg/m2
1 hour
Day 8
IV
135 mg/m2
IV
3 hours
Day 1
60 mg/m2
IP
By gravity as rapidly
as possible
Day 8
75 mg/m2
IP
By gravity as rapidly
as possible
Day 1
135 mg/m2
IV
3 hours
Day 1
60 mg/m2
IP
By gravity as rapidly
as possible
Day 8
IP
By gravity as rapidly
as possible
2
Cisplatin
Paclitaxel
Carboplatin
Duration
AUC 5
if measured GFR
(use AUC 6 if calculated
GFR)
Paclitaxel
3
Route
AUC 5
if measured GFR
(use AUC 6 if calculated
GFR)
* or according to local practice
Repeat
Day 1
30 minutes*
Day 1
Every
21 days
Phase III
Patients will be randomized to one of the following two arms:
Schedule
Arm
Agent(s)
Dose
Route
Duration
Days
135 mg/m2
3 hours
Day 1
60 mg/m2
1 hour
Day 8
Repeat
Paclitaxel
1
Carboplat
in
2
Every
21 days
IV
AUC 5
if measured GFR
(use AUC 6 if calculated GFR)
30 minutes*
The selected IP arm from Phase II (regimen as in above table)
* or according to local practice
Day 1
Every
21 days
DDPC-PREOC
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
?
Trial Design
250
patients
with
platinum
resistant
disease
R
A
N
D
O
M
I
S
E
Carboplatin (AUC 3) and
paclitaxel (80 mg/m2) for 3
weeks out of 4 for 6 cycles
Primary Endpoint: PFS
Pegylated Liposomal
Doxorubicin (40 mg/m2)
every 4 weeks for 6 cycles
Secondary Endpoints:
Overall Survival
Quality of Life
Health Economic Analysis
Response Rate
Toxicity/Hypersensitivity
Dose Intensity
Post progression therapy
Thank you for attention