GCIG Cervix Committee:
Prague 2010
William Small Jr.
Satoru Sagae
Activity Since Chicago
• Conference calls were held in July and
September
• Separate radiotherapy calls were accomplishe
d to finalize the radiotherapy section for the
upcoming ANZGOG outback trial.
• Significant progress was made on completing
open trials and developing concepts.
Publications/Presentations
Kitchener H.C., Thomas G., Hoskins W.,
Small W. Jr.
,
Trimble, E.L. on behalf of the Cervical Cancer
Consensus Group. The Development of Priority Cervi
cal Cancer Trials: A Gynecologic Cancer InterGroup
Report. Int J Gyn Can, 20(6):1092-1100, August 201
0.
Viswanathan, A.N., Creutzberg, C., Craighead, P., McCor
mack, M., Toita, T., Narayan, K., Reed, N., Long, H., Ki
m, H.J., Marth, C., Lindegaard, J., Cerrotta, A., Small,
W Jr., Trimble, E. Brachytherapy Practice Patterns in t
he Gynecologic Cancer Intergroup. In Press, Int J Ra
diol Oncol Biol Phys, 2010.
ACTIVE GCIC TRIALS
Confidential
Month
Jul
May
Mar
Jan
Nov
Sep
Jul
May
Mar
Jan
Nov
Sep
Jul
May
Mar
Jan
Nov
Cumulative Pts No.
Japan: 151 / 200 pts (75.5%)
Korea: 71 / 100 pts (71.0%) Arm SP: 126pts
30 Taiwan: 32 / 60 pts (53.3%) Arm P: 128pts (not treated: 7pts)
27
28
26
350
Total:
254
/
360
pts
(70.3%)
26
23
23
24
300
21
22
20
20
20
20
250
18
18
18
15
15
16
200
14
13
1313
1313
14
11 1211
11
11 11
12
150
10
9
9
9
10
88 8
8
100
66
6
4 44
3
4
50
22
2
1
1
2
00 00 00 00 00 00 00 00 00 00 00 00 00 00 00
0
0
Sep
Pts No./Month
S-1+CDDP vs single agent CDDP
Phase3 study in Cervical cancer (IVB/Rec)
Patient enrollment status (01/Jun/2010)
Confidential
JGOGDT-104/GCIG S-1 Trial
Accrual
Total 338
Japan 208, Korea 86, Taiwan 44
GOG 240
(GOG 204 Replacement)
• 2 x 2 Factorial Design
– First randomization:
Winner of GOG 204 (Cisplatin +
Paclitaxel)
vs
Topotecan + Paclitaxel
– Second Randomization: Bevacizumab
vs
No Bevacizumab
• Primary Endpoint = survival, superiority trial (30% reducti
on in HR)
KS Tewari Study Chair
• Accrual Goal = 450 patients
GOG 263
Randomized Phase III Clinical Trial of Adjuvant
Radiation vs Chemoradiation In Intermediate Risk,
Stage I/IIA Cervical Cancer Treated With Initial
Radical Hysterectomy and Pelvic
Lymphadenectomy
Sang Young Ryu, M.D.
Korea Cancer Center Hospital
Seoul, Korea
GOG 263
Control Arm; Radiation therapy
Stage I-IIA
Radical hysterectomy+BPLND
>2 of intermediate risk factors
Randomization
Cervical cancer
CRT Arm; Weekly CDDP
40mg/m2 concurrent to radiation
RTOG-0724 (GOG):
ChemoRT with and without
adjuvant chemotherapy in
high risk cervix cancer after
hysterectomy
Developing Concepts –
Discussions
THE OUTBACK TRIAL
A Phase III trial of adjuvant chemotherapy
following chemo-radiation as primary treatment
for locally advanced cervical cancer compared to
chemo-radiation alone
Design: International randomized phase III study
Countries that have expressed interest
ANZ (18 sites)
Canada (NCIC)
USA (GOG and RTOG)
Spain (GEICO)
Brazil
India
Romania
Netherlands (DCGOG)
Timelines
• Lead HREC approval:
Aug 2010
- administrative amendment just approved
• CTEP approval of concept: Aug 2010
• CRFs finalized:
Sept 2010
- database development in process
•
•
•
•
First ANZ site open:
First patient on study:
Last patient on study:
Follow-up completed:
Dec 2010
Dec 2010
Dec 2014
Dec 2019
the SHAPE Trial:
Simple Hysterectomy And Pelvic node dissection in Early cervix cancer
Comparing radical hysterectomy and pelvic node
dissection against simple hysterectomy and pelvic
node dissection in patients with low risk cervical
cancer
Chair: Marie Plante
Laval University, Quebec City
An NCIC Clinical Trials Group proposal for the Gynecological Ca
ncer Inter Group (GCIG)
Prague - October 2010
SHAPE trial

Background


Rad hyst/nodes:
standard
treatment
Acute/long term
side effects: 2030%

Low risk disease



< 2cm & < 50% stromal invasio
n
Risk of parametrial infiltration <
1%
Less radical surgery (simple hy
st + nodes) may be be adequat
e treatment



< 5% pelvic relapse rate
Success of salvage therapy in
65% (RT/SX)
Overall survival should not be c
ompromised
SHAPE trial

Objective:


To show that simple hysterectomy in low risk cervix
cancer is safe and is associated with less morbidity
than radical surgery
AND that overall survival will not be significantly
different (between RHPND and SHPND) even if a
slightly higher relapse rate occurs in the latter group
 Primary endpoint

Compare the 3-year pelvic recurrence rate between
radical and simple hysterectomy patients
Patient Population
Stage IA2-IB1 Cervix cancer
Squamous , Adeno & Adenosquamous ca
< 2cm and < 50% stromal invasion
Grades 1,2 & 3
MRI/ CT node negative
RANDOMIZATION
Control Arm
Radical Hysterectomy &
PLND* +/- SLN Mapping**
Stratification
Centers (performing SN mapping vs not
)
Mode of surgery (abd vs non-abd route
)
Stage (IA2 vs IB1)
Histology (squamous vs adenoca)
Grade (1-2 vs 3)
Experimental Arm
Simple Hysterectomy with
Upper Vaginectomy &
PLND* +/- SLN Mapping**
Post surgical quality of life & disease outc
omes measured 3 monthly X 2 years, and
6 monthly for further 3 years
* PLND – Pelvic lymph node dissection
**SLN - Sentinel lymph node mapping optio
nal
the SHAPE Trial: International collaborators
Co-op groups
AGO-Austria
AGO-Germany
ANZGOG-Australia
GEICO-Spain
MRC/NCRI-England
NSGO-Scandinavia
SGCTG-Scotland
SGOG-China
Specialty groups
Belarus
Czech Republic
Latria
Lithuania
Romania
Serbia
INduction ChemoThERapy in
Locally Advanced CErvical
Cancer-INTERLACE
Mary McCormack
for the NCRI Gynaecological Clinical
Studies Group
GCIG Prague Oct 2010
INTERLACE
A phase III trial of
weekly, dose dense, induction
chemotherapy
followed by
chemoradiation versus
chemoradiation alone
in locally advanced cervical cancer
INTERLACE - Phase 3 trial
Randomise
Carboplatin AUC2 &
Paclitaxel 80mg/m2
Standard CRT
Weeks 1-6
Standard CRT : 40—50.4Gy in 20-28 fractions plus
Weeks 7 – 13
Standard CRT
Intracavity brachytherapy to give min total EQD2 d
ose of 74-80Gy to point A/volume.
Weekly cisplatin 40mg/m2 x 6 weeks
Follow-up
3 monthly for 2 years; 6 monthly for 3 years
Proposal- Current Status
•Full Proposal for funding submitted August
decision expected early November 2010
•Open to recruitment –June/July 2011
•Collaborators- UK ( 22 )
Eire ( 2 )
France
India (1)
South Africa (2)
Contact: Lindsay James
Cancer Research UK and UCL Cancer Trials Centre
l.James@ctc.ucl.ac.uk
A phase III trial comparing efficacy
and cost-effectiveness between
Weekly and Three-Weekly cisplatin
Chemotherapy for Chemoradiation in
Cervical Cancer
An international, multi-center, randomized Phase III
GCIG trial led by TGCS, KGOG (TAKO)
Schema
Control Arm; Weekly Cisplatin
40mg/m2 6 cycles
Locally advanced cervical
cancer
Stage IIB-IVA
Randomization
Cervical cancer
Study Arm; Tri-weekly Cisplatin
75mg/m2 3 cycles
Principal Investigator:
Dr. Sarikapan Wilailak
Faculty of Medicine Ramathibodi Hospital, Mahidol
university, Bangkok, Thailand
Principal Investigator:
Dr. Sang Young Ryu
Korea Cancer Center Hospital
Seoul, Korea
Cervical cancer in
underdeveloped nations
Proposal for GCIG Cervix
Cancer Network of Trial
Centres in non-GCIG
Countries
Clinical Trial Summary
• One trial looking at less radical surgery in low risk cervical cance
r patients.
• Two advanced/recurrent randomized trials.
• One trial looking at chemo/RT vs. RT alone after hysterectomy in
intermediate risk patients.
• Three trials investigating adjuvant chemotherapy in high risk cerv
ical cancer.
– +/- Neoadjuvant than chemo/RT.
– Post-hysterectomy chemo/RT+/- adjuvant chemo
– Chemo/RT +/- adjuvant chemo
• One limited resource trial looking at reduced frequency of concu
rrent cisplatin in chemo RT patients
Goals
• Activate developing trials.
• Foster collaboration and rapid accrual
to open trials
• Develop a working group to help
advance therapy in underdeveloped
countries.
Please attend the site
specific trials