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 accomplished 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 Cervical Cancer Trials: A Gynecologic Cancer InterGroup Report.  Int J Gyn Can, 20(6):1092-1100, August 2010.

Viswanathan, A.N., Creutzberg, C., Craighead, P., McCormack, M., Toita, T., Narayan, K., Reed, N., Long, H., Kim, H.J., Marth, C., Lindegaard, J., Cerrotta,

A., Small, W Jr., Trimble, E. Brachytherapy Practice Patterns in the Gynecologic Cancer Intergroup. In Press, Int J Radiol Oncol Biol Phys, 2010.

ACTIVE GCIC TRIALS

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S-1+CDDP vs single agent CDDP Phase3 study in Cervical cancer (IVB/Rec)

Patient enrollment status (01/Jun/2010)Japan: 151 / 200 pts (75.5%)Korea: 71 / 100 pts (71.0%)Taiwan: 32 / 60 pts (53.3%)

Total: 254 / 360 pts (70.3%)

Arm SP: 126ptsArm P: 128pts 　 (not treated: 7pts)

Confidential

JGOGDT-104/GCIG S-1 Trial Accrual

Total 338Total 338Japan 208, Korea 86, Taiwan 44Japan 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% reduction in HR)

• Accrual Goal = 450 patients KS Tewari Study Chair KS Tewari Study Chair

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

Cervical cancer Cervical cancer

Stage I-IIAStage I-IIARadical hysterectomy+BPLNDRadical hysterectomy+BPLND >>2 of intermediate risk factors2 of intermediate risk factors

Control Arm; Radiation therapyControl Arm; Radiation therapy

CRT Arm; Weekly CDDP CRT Arm; Weekly CDDP 40mg/m40mg/m22 concurrent to radiationconcurrent to radiation

Random

izationR

andomization

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: Dec 2010• First patient on study: Dec 2010• Last patient on study: Dec 2014• Follow-up completed: 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 Chair: Marie Plante Laval University, Quebec CityLaval University, Quebec City

An NCIC Clinical Trials Group proposal for the Gynecological An NCIC Clinical Trials Group proposal for the Gynecological Cancer Inter Group (GCIG)Cancer Inter Group (GCIG)

Prague - October 2010Prague - October 2010

SHAPE trial Background

Rad hyst/nodes: standard treatment

Acute/long term side effects: 20-30%

Low risk diseaseLow risk disease < 2cm & < 50% stromal < 2cm & < 50% stromal

invasioninvasion Risk of parametrial Risk of parametrial

infiltration < 1%infiltration < 1% Less radical surgery (simple Less radical surgery (simple

hyst + nodes) may be be hyst + nodes) may be be adequate treatment adequate treatment

< 5% pelvic relapse rate< 5% pelvic relapse rate Success of salvage therapy Success of salvage therapy

in 65% (RT/SX)in 65% (RT/SX) Overall survival should not Overall survival should not

be compromisedbe compromised

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 PopulationPatient Population Stage IA2-IB1 Cervix cancerStage IA2-IB1 Cervix cancer

Squamous , Adeno & Adenosquamous caSquamous , Adeno & Adenosquamous ca < 2cm and < 50% stromal invasion< 2cm and < 50% stromal invasion

Grades 1,2 & 3Grades 1,2 & 3MRI/ CT node negativeMRI/ CT node negative

RANDOMIZATIONRANDOMIZATION

Control　ArmControl　ArmRadical　Hysterectomy　&　Radical　Hysterectomy　&　

PLND*　+/-　SLN　PLND*　+/-　SLN　Mapping**Mapping**

Experimental　ArmExperimental　ArmSimple　Hysterectomy　withSimple　Hysterectomy　with

Upper　Vaginectomy　&　Upper　Vaginectomy　&　PLND*　+/-　SLN　Mapping**PLND*　+/-　SLN　Mapping**

Post surgical quality of life & disease Post surgical quality of life & disease outcomes measured 3 monthly X 2 outcomes measured 3 monthly X 2 years, and 6 monthly for further 3 years, and 6 monthly for further 3 yearsyears

* PLND – Pelvic lymph node dissection* PLND – Pelvic lymph node dissection**SLN - Sentinel lymph node mapping **SLN - Sentinel lymph node mapping optionaloptional

SStratification tratification Centers (performing SN mapping vs Centers (performing SN mapping vs not)not)Mode of surgery (abd vs non-abd Mode of surgery (abd vs non-abd route)route)Stage (IA2 vs IB1)Stage (IA2 vs IB1)Histology (squamous vs adenoca)Histology (squamous vs adenoca)Grade (1-2 vs 3)Grade (1-2 vs 3)

the SHAPE Trial: International collaborators

Co-op groups Specialty groups AGO-Austria BelarusAGO-Germany Czech Republic ANZGOG-Australia LatriaGEICO-Spain LithuaniaMRC/NCRI-England RomaniaNSGO-Scandinavia Serbia SGCTG-Scotland SGOG-China

INduction　ChemoThERapy　in　　Locally　Advanced　

CErvical　Cancer-INTERLACE

Mary McCormack for the NCRI Gynaecological Clinical

Studies Group GCIG Prague Oct 2010GCIG Prague Oct 2010

INTERLACEA　phase　III　trial　of　weekly,　dose　dense,　induction　chemotherapy　followed by chemoradiation　versus　chemoradiation　alonein　locally　advanced　cervical　cancer

INTERLACE　-　　Phase　3　trial

RandomiseRandomise

Carboplatin AUC2 & Carboplatin AUC2 & Paclitaxel 80mg/mPaclitaxel 80mg/m22

Weeks 1-6Weeks 1-6

Weeks 7 – 13Weeks 7 – 13Standard CRTStandard CRT

Standard CRTStandard CRT

Follow-upFollow-up3 monthly for 2 years; 6 monthly for 3 years3 monthly for 2 years; 6 monthly for 3 years

Standard CRT :Standard CRT : 40—50.4Gy in 20-28 fractions plus 40—50.4Gy in 20-28 fractions plus Intracavity brachytherapy to give min total EQD2 Intracavity brachytherapy to give min total EQD2 dose of 74-80Gy to point A/volume.dose of 74-80Gy to point A/volume.Weekly cisplatin 40mg/mWeekly cisplatin 40mg/m22 x 6 weeks x 6 weeks

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 JamesContact: Lindsay JamesCancer Research UK and UCL Cancer Trials CentreCancer Research UK and UCL Cancer Trials Centrel.James@ctc.ucl.ac.ukl.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 An international, multi-center, randomized Phase III GCIG trial led by TGCS, KGOG GCIG trial led by TGCS, KGOG (TAKO)(TAKO)

Schema

Cervical cancer Cervical cancer

Locally advanced cervical Locally advanced cervical cancer cancer Stage IIB-IVAStage IIB-IVA

Control Arm; Weekly Cisplatin Control Arm; Weekly Cisplatin 40mg/m2 6 cycles40mg/m2 6 cycles

Study Arm; Tri-weekly Cisplatin Study Arm; Tri-weekly Cisplatin 75mg/m2 3 cycles75mg/m2 3 cycles

Random

izationR

andomization

Principal Investigator:

Dr. Sarikapan Wilailak

Faculty of Medicine Ramathibodi Hospital, Mahidol university, Bangkok, Thailand

Principal Investigator:

Dr. Sang Young Ryu

Korea Cancer Center HospitalSeoul, 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 cancer 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 cervical cancer.– +/- Neoadjuvant than chemo/RT.– Post-hysterectomy chemo/RT+/- adjuvant chemo– Chemo/RT +/- adjuvant chemo

• One limited resource trial looking at reduced frequency of concurrent 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