EORTC 55971
Upfront Surgery
vs
Neoadjuvant Chemotherapy
Patients
closed / 550
Leading
EORTC
Participating
NCIC CTG
Presentated at IGCS 2008
Tarceva Trial EORTC 55041
Tarceva consolidation 2 years
Primary Chemotherapy
Control
Patients
closed / 835
Leading
EORTC
Participating
AGO-AUSTRIA, ANZGOG, GINECO,
MRC/NCIC, MANGO
ICON-7
TC
±
BEVACIZUMAB
Patients
closed / 1520
Leading
MRC/NCRI
Participating
NCIC CTG, AGO OVAR, GINECO, GEICO
EORTC, ANZGOG, NSGO
GOG 218
CT vs CT + Bevacizumab
Placebo vs
CT + Bevacizumab concurrent and extended
Patients
closed / 1800
Leading
GOG
Participating
ECOG, NCCTG, NSABP, SWOG
10
Phase III Trial of Bevacizumab in the Primary
Treatment of Advanced Epithelial Ovarian,
Primary Peritoneal, or Fallopian Tube Cancer:
A Gynecologic Oncology Group (GOG) Study
R.A. Burger,1 M.F. Brady,2 M.A. Bookman,3
J.L. Walker,4 H.D. Homesley,5 J. Fowler,6
B.J. Monk,7 B.E. Greer,8 M. Boente,9 S.X. Liang10
1Fox
Chase Cancer Center, Philadelphia, PA; 2Gynecologic Oncology Group Statistical
and Data Center, Roswell Park Cancer Institute, Buffalo, NY; 3University of Arizona
Cancer Center, Tucson, AZ; 4University of Oklahoma Health Sciences Center,
Oklahoma City, OK; 5Brody School of Medicine, Greenville, NC; 6James Cancer
Hospital at the Ohio State University, Hilliard, OH; 7University of California, Irvine
Medical Center, Orange, CA; 8Seattle Cancer Care Alliance, Seattle, WA; 9Minnesota
Oncology and Hematology, Minneapolis, MN; 10State University of New York at Stony
Brook, Stony Brook, NY, USA
11
GOG-0218: Investigator-Assessed PFS
Proportion surviving progression free
1.0
0.9
Patients with event, n (%)
0.8
Arm I
CP
(n=625)
Arm II
CP + BEV
(n=625)
Arm III
CP + BEV  BEV
(n=623)
423
(67.7)
418
(66.9)
360
(57.8)
10.3
11.2
14.1
0.908
(0.759–1.040)
0.717
(0.625–0.824)
0.080*
<0.0001*
Median PFS, months
0.7
Stratified analysis HR
(95% CI)
0.6
One-sided p-value (log rank)
0.5
0.4
0.3
0.2
CP (Arm I)
+ BEV (Arm II)
0.1
+ BEV → BEV maintenance (Arm III)
0
0
12
24
Months since randomization
36
*p-value boundary = 0.0116
GOG0252: IP Therapy
• Epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer
• Optimal and Suboptimal Disease (through April 2011)
• Primary Endpoint: PFS
I
Carboplatin AUC=6 (IV)
Paclitaxel 80 mg/m2 IV (d1,8,15)
Bevacizumab (C2-6)
Bevacizumab
q21d x 16
II
Carboplatin AUC=6 (IP)
Paclitaxel 80 mg/m2 (d1,8,15)
Bevacizumab (C2-6)
Bevacizumab
q21d x 16
III
Cisplatin 75 mg/m2 (IP)
Paclitaxel 135 mg/m2 (d1, 3h)
Paclitaxel 60 mg/m2 (d8, IP)
Bevacizumab (C2-6)
Bevacizumab
q21d x 16
Open:
27-Jun-09
Closed:
(ongoing)
Target Accrual: 1250 pts
Walker J. for GOG, pending
GOG0262: Dose-Dense Integration
• Epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer
• Suboptimal residual disease
• Primary Endpoint: PFS
I
Carboplatin AUC=6
Paclitaxel 80 mg/m2 (d1,8,15)
+/- Bevacizumab (C2-6)$
Bevacizumab
q21d$
II
Carboplatin AUC=6
Paclitaxel 175 mg/m2 (d1)
+/- Bevacizumab (C2-6) $
Bevacizumab
q21d$
$ Use
of Bevacizumab to be determined by patient and
physician choice prior to randomization
Open:
27-SEP-10
Closed:
--Target Accrual: 1100 pts
Chan J. for GOG, pending
OCEANS: CG +/- Bevacizumab
•
•
•
•
•
Recurrent epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer
Platinum-Free Interval stratified 6-12 vs >12 months
Industry-sponsored multicenter phase II amended to phase III
Primary Endpoint: PFS with RECIST
Secondary Endpoints: OS, GI perforation event rate
I
Gemcitabine 1000 mg/m2 d1,8
Carboplatin AUC=4.0 d1
Placebo IV d1
x6
Placebo q21d
(until PD)
II
Gemcitabine 1000 mg/m2 d1,8
Carboplatin AUC=4.0 d1
Bevacizumab 15 mg/kg IV d1
x6
Bevacizumab q21d
(until PD)
Open:
Apr-07
Closed:
Jan-10
Target Accrual: 483 pts
Aghajanian C, et al. (under analysis)
GOG 0213: Secondary Cytoreduction
• Epithelial Ovarian, Fallopian, or Peritoneal Cancer
• One prior therapy, Platinum-free interval > 6 months
• Primary Endpoint: OS
Carboplatin AUC=5
A Paclitaxel 175 mg/m2
Maximal
I
Secondary
Cytoreduction
R1
II
No
Secondary
Surgery
Not Surgical
III Candidate
x 6-8
(No further therapy)
R2
Carboplatin AUC=5
B Paclitaxel 175 mg/m2 x 6-8
Bevacizumab 15 mg/kg
Bevacizumab 15 mg/kg
(Until progression)
Open:
06-Dec-07
Closed:
Ongoing
Target Accrual: 660 pts
Coleman, et al. 2008
GOG212: Ovarian Maintenance
•
•
•
•
Epithelial Ovarian or Primary Peritoneal Cancer
Optimal or Suboptimal Cytoreduction
Clinical CR with normal CA125, no symptoms, normal CT
Primary Carboplatin and Paclitaxel (or Docetaxel), 5-6 cycles
Primary Rx:
Carboplatin
and Taxane
(5-6 Cycles)
I PG-Paclitaxel 175 mg/m2 (15 m), q28d
x 12
II Paclitaxel 175 mg/m2 (3 h), q28d
x 12
III Observation
Open:
Mar-05
Closed:
--Target Accrual: 1550 pts (3.5 Y+)
Markman, et al. for GOG
CALYPSO
Published Ahead of Print on May 24, 2010
AGO-OVAR-9
Carbo Paclitaxel +/- Gemcitabine
Patients
closed 1742
Leading
AGO-OVAR
Participating
GINECO, NSGO,
SCOTROC 4
Carbo Flat Dosing vs Intrapatient Dose Escalation
Patients
Leading
closed 932
SGCTG
Participating
ANZGOG
Manuscript in preparation
HECTOR
Carbo Topo vs Chemo (CT or CG) in recurrent
Platinum-sensitive ovarian cancer
Patients
closed 550
Leading
NOGGO/AGO-OVAR
Participating
AGO-AUSTRIA, GEICO
AGO-OVAR-OP.2 DESKTOP II
Evaluation of predictive factors for complete
resection in platinum-sensitive recurrent
ovarian cancer
Patients
closed/412
Leading
AGO-OVAR
Participating
AGO-AUSTRIA, MITO,
selected Canadian+Australian
centers
Report
IGCS 2008, resubmitted
AGO-OVAR 16
Amendment: 2 years of consolidation
Pazopanib consolidation 1 yr
First Line Chemotherapy
Control
Patients
941 / 900
Leading
AGO-OVAR
Participating
AGOAustria, ANZGOG, BGOG, GEICO, GINECO, ICORG,
JGOG, KGOG, MANGO, MITO, NSGO, US-Sites: California
Consortium, NY GOG, SWOG
AGO-OVAR-12
Carbo Paclitaxel +/- BIBF 1120 (Vargatef)
Patients
Leading
525 / 1300 (2:1 random)
AGO-OVAR
Participating AGO-Austria, BGOG, GINECO,
MANGO, MITO, NSGO, US Oncology
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
284/640
no Lymphadenectomy
no bulky lymph nodes
Endpoints: OS, PFS, QoL
Strata: centre, PS ,age
Supported by Deutsche Forschungsgemeinschaft
JGOG-3017 Clear Cell Carcinoma
CT
vs
CDDP + Irinotecan
Patients
597/662
Leading
JGOG
Participating
GINECO, GOG, KGOG,
MITO, SGCTG
JGOG-3019 iPocc
C(3w, IV)T(1w , IV)
vs
Patients
3/746
Leading
JGOG
Participating
?
C(3w , IP)T(1w , IV)
MITO-7
Weekly CT vs 3-weekly CT (QoL)
Patients
315 / 650
Leading
MITO
Participating
MaNGO
MITO-8
LipDox vs CT cross-over
in 6-12 m platinum-free interval
Patients
72 / 253
Leading
MITO
Participating
MaNGO, AGO-OVAR
AURELIA
Bevacizumab plus chemotherapy vs chemotherapy
alone in patients with platinum-resistant EOC
Patients
226 / 332
Leading
GINECO
Participating
AGO-OVAR, GEICO, MITO,
NSGO, BGOG, DGOG
INOVATYON
Relapsed ovarian cancer
with platinum-free interval (PFI) of 6-12 months
Randomization
(strata: ECOG, Measurable disease, PFI)
PLD 30 mg/m2 1 hour i.v. + Carboplatin AUC 5
30-60 min i.v. on day 1 q4weeks
Up to 6 cycles or progression
PLD 30 mg/m2 1 hour i.v. + Trabectedin 1.1
mg/m2 3 hoour i.v. on day 1 q3weeks
Up to 6 cycles or progression
3rd line chemotherapy: at investigator discretion
3rd line chemotherapy: platinum rechallenge
Dipartimento di Oncologia - Istituto “Mario Negri” - Milano
AGO-OVAR-OP.4 DESKTOP III
Cytoreductive surgery vs NO surgery
in platinum-sensitive recurrent EOC
Patients
3 / 385 activated July 1
Leading
AGO-OVAR
Participating
?
MucinousEOC
oxaliplatin + capecitabine ± bevacizumab
vs carboplatin + paclitaxel ± bevacizumab
Patients
0/332
Leading
NCRI/SGCTG GOG
Participating
AGO OVAR, GINECO, MaNGO,
NSGO, KGOG
ICON 8
C3w P3w vs C3w P1w vs C1w P1w
Patients
1485
Leading
MRC
Participating
??
NCIC CTG OV.21
IP/IV Platinum/P vs IV CP
optimally debulked following NACT
Patients
0 / 780
Leading
NCIC CTG
Participating
GEICO, NCRI, SWOG
Thank you for attention