GCIG Cervix Committee:
Chicago 2010
William Small Jr.
Satoru Sagae
Activity Since Belgrade
• Conference calls were held on 1/19/10, 2/16/
10, 4/10/10
• Separate GCIG call to discuss RT on the
OUTBACK trial.
• Significant progress was made on developing
trails.
• We have a lot to discuss – please keep on tim
e and remember there are further discussions
planned for tomorrow for a number of the trial
s.
ACTIVE/NEAR ACTVIE 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)
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
(GOG 92 Replacement)
Stage IA2-IB2: La
rge, deeply invasi
ve tumors with va
scular invasion li
mited to the cervi
x after radical hys
terectomy
PI = SANG YOUNG RYU
N = 480
Primary Endpoint = RFS
Pelvic Radiation
R
A
N
D
O
M
I
Z
E
Pelvic Radiation and
Weekly cisplatin
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, RTOG)
Spain (GEICO)
Norway (NSGO)
India
Romania
Netherlands (DCGOG)
Timelines
•
•
•
•
•
Lead HREC approval: July 2010
First ANZ site open: Sept 2010
First patient on study: Sept 2010
Last patient on study: Sept 2014
Follow-up completed: Sept 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
University of Laval, Quebec City
An NCIC Clinical Trials Group proposal for the Gynecological
Cancer Inter Group (GCIG)
Patient Population
Stage IA2-IB1 Cervix cancer
Squamous , Adeno & Adenosquamous ca
< 2cm and < 50% stromal invasion
Grades 1,2 & 3
MR/ 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
outcomes measured 3 monthly X 2 years,
and 6 monthly for further 3 years
* PLND – Pelvic lymph node dissection
**SLN - Sentinel lymph node mapping optional
the SHAPE Trial: Its goal

To show that simple hysterectomy in low risk cervix
cancer patients is safe and is associated with less
morbidity than radical surgery:

AND that overall survival will not be significantly different for
RHPND or 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
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
Chemoradiation for Locally
Advanced Cervical Cancerwhat next?
Mary McCormack
NCRI Gynaecological Clinical Studies
Group
Proposed Phase 3 trial in LACC
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
Intracavitary brachytherapy to give total EQD2
dose 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
Randomized Clinical Trial of Weekly
versus Tri-Weekly Cisplatin based
Chemoradiation in Locally Advanced
Cervical Cancer
Sang Young Ryu, MD
Korea Cancer Center Hospital
Seoul, Korea
Challenging Trial to Weekly Cisplatin
Weekly Cisplatin vs Tri-Weekly Cisplatin
; KCCH clinical trial
Weekly Cisplatin vs Tri-Weekly Cisplatin
; KCCH clinical trial
• 2002-2004
• 105 patients
– Stage IIB-IVA
• Arm 1: Weekly cisplatin 40mg/m2
• Arm 2: Tri-weekly cisplatin 75mg/m2
• Primary end point; compliance
– Percentage of completed cycle
– Treatment delay
Long term outcome of Weekly vs Tri-weekly Cisplatin
based chemoradiation in locally advanced cervical cancer
5YSR (n=105)
88% (Tri-weekly)
66% (Weekly)
HR 0.375
95% CI(0.154-0.914)
p=0.03
Weekly versus Tri-weekly Cisplatin
based Chemoradiation
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
Weekly versus Tri-weekly Cisplatin
based Chemoradiation
• Primary end-point
– 5-year survival rate
• Secondary endpoint
– Compliance, Toxicity profile
• Statistics
– 15% increase of 5 YSR (65-> 80%)
– 10% loss
– Total; 500
Cervical cancer in
underdeveloped nations
IEO
Neoadjuvant
Chemotherapy followed
by Exenteration in
Cervical Cancer
EUROPEAN INSTITUTE
OF ONCOLOGY
MILAN (slides courtesy of
Fabio Landoni, MD)
IEO
Proposed Trial
Title:
“A
prospective
trial
of
neoadjuvant
chemotherapy prior to pelvic exenteration for patients
with bulky (> 5 cm) locally recurrent cervical carcinoma.”
 Primary Objective: To evaluate the response rate of
neoadjuvant chemotherapy (TIP X 3) prior to planned
pelvic exenteration in patients with bulky (> 5 cm) locally
recurrent cervical carcinoma.
 Secondary Objective: To evaluate toxicity of the
neoadjuvant chemotherapy regimen, ability to attain
negative surgical margins in the exenteration specimen,
and determine disease-free and overall survival.

Proposal for GCIG Cervix
Cancer Network of Trial
Centres in non-GCIG
Countries
ACRIN6671-GOG0233Utility of Preoperative FDG-PET/CT
Prior to Primary Chemoradiation Therapy to Detect Retroper
itoneal Lymph Node Metastasis in Patients With Locoregiona
lly Advanced Carcinoma of the Cervix (IB2, IIA =4 CM, IIB-I
VA) or Endometrium (Grade 3 Endometrioid Endometrial Ca
rcinoma; Serous Papillary Carcinoma, Clear Cell Carcinoma
, or Carcinosarcoma (Any Grade); and Grade 1 or 2 Endome
trioid Endometrial Carcinoma With Cervical Stromal Involve
ment Overt in Clinical Examination or Confirmed by Endocer
vical Curettage)
HYCAR
Oral topotecan plus Carboplatin
in advanced or relapsing cervix cancer.
A phase II GINECO trial
JE Kurtz, on behalf of the GINECO group
Actions undertaken
 Treatment discontinued (for toxicity) in 4 patients, 2 pts
continued at reduced dosing
 Treatment discontinued for progression/refusal in 3/1
patients
 Overall, dose reduction (Carbo AUC 4, Topo 2.7mg/m2)
occurred in 5/8pts
 The safety committee advised to stop the study in view
of unacceptable toxicity
CONCLUSIONS
• We continue to build on the Cervical SOTS Clinical
Trials Meeting
• Four current active trials
– Two chemotherapy trials for recurrent
advance
- recurrent disease.
– Two adjuvant trials.
• One less aggressive surgical trial in development.
• Three locally advanced trials in development.
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