Endometrial Cancer Commitee Minutes Chicago June 3, 2010 David Miller, Ketta Lorusso

Endometrial Cancer Commitee Agenda Chicago June 3, 2010 PROPOSED GCIG STUDIES FOR REVIEW STAGING LYTEC LYmphadenectomy Trial in Endometrial Cancer

Treatment Algorithm

Participating Institutions Endorsed by ENGOT 2/2010 AGO AustGROIN EORTC GCG ICORG BGOG MANGO GEICO MITO HECOG NCRI GINECO NOGGO NSGODGC JGOGKGOG TRSGO

Endometrial Cancer Commitee Agenda Chicago June 3, 2010 PROPOSED GCIG STUDIES FOR REVIEW ADVANCED/RECURRENT NCIC CTG EN8 Randomized Phase III trial on Progestational Hormone Therapy vs Deferolimus in women with recurrent or metastatic endometrial cancer

Schema Sample size: Approximately 460 patients Arm 2: medroxy progesterone 200 mg or megestrol 160 mg (as per local practice) po daily Chemotherapy options Survival follow-up Disease progression Imaging q 8 weeks Arm 1: ridaforolimus 40 mg po days 1-5 each week RANDOMIZERANDOMIZE Women with recurrent or metastatic endometrial cancer 1-2 Prior Chemotherapy

EN.8 - A PHASE III STUDY OF STANDARD THERAPY VERSUS RIDAFOROLIMUS IN WOMEN WITH RECURRENT OR METASTATIC ENDOMETRIAL CANCER WHO HAVE PREVIOUS HAD CHEMOTHERAPY Interested groups: ACRIN, AGO-AUST, AGO-OVAR, ANZOG, DGOG, EORTC, GEICO, GINECO, JGOG, MANGO, MITO, NCRI, NSGO, SWOG

Endometrial Cancer Commitee Agenda Chicago June 3, 2010 PROPOSED GCIG STUDIES FOR REVIEW TROPHOBLASTIC NEOPLASIA ANZGOG : 1. CHM with negative HCG 8 weeks post evacuation 2. PHM reaching negative HCG Cross registry analysis or randomized trial of current local policy FU vs discontinuation of FU according to the above findings. End point: comparison of incidence of persistent GTN in either arms. To be presented in Prague

Endometrial Cancer Commitee Agenda Chicago June 3, 2010 PROPOSED GCIG STUDIES FOR REVIEW TROPHOBLASTIC NEOPLASIA GOG UC 1005 A sequential phase II/III randomized trial comparing 3 widely used regimens for the management of low risk Gestational Trophoblastic Neoplasia

Potential clinical trials in Gestational Trophoblastic Neoplasia Concept of a multi-centred, randomised double-blind trials discussed at ISSTD in Cochin Support for potential trials in low risk GTN and 2 nd line chemotherapy for high risk GTN –Low risk – GOG –2 nd line high risk NCRI

A randomized trial comparing three widely used regimens for the management of low risk gestational trophoblastic neoplasia –UC1005 Potential trial arms 8 day 50mg I.M. MTX with folinic acid rescue 5 day 125mg/m 2 I.V. MTX Biweekly dactinomycin 1.25mg/m 2 I.V All arms QOL assessment Would a two arm trial 8 day MTX vs Act-D be better?

2 nd line treatment for high risk GTN EP-EMA (etoposide,cisplatin – etoposide,methatrexate, act-D) vs TP/TE (taxol,cisplatin vs taxol,etoposide) Mike Seckl at Charing Cross Hospital is leading through NRCI-UK process Again would probably need support through GCIG, GOG ANZGOG etc

Endometrial Cancer Commitee Agenda Chicago June 3, 2010 PROPOSED GCIG STUDIES FOR REVIEW TROPHOBLASTIC NEOPLASIA GOG UC 1005 A sequential phase II/III randomized trial comparing 3 widely used regimens for the management of low risk Gestational Trophoblastic Neoplasia (John Tidy: Interested groups: AGO Aust., JGOG,

Endometrial Cancer Commitee Agenda Chicago June 3, 2010 UPDATE ON ACTIVE STUDIES AGO AGO-GYN 5 Antitumoral activity and safety of AEZS-108 in women with LHRH receptor positive gynecological tumors

Endometrial Cancer Commitee Agenda Chicago June 3, 2010 UPDATE ON ACTIVE STUDIES: GOG GOG-0238 A randomized trial of Pelvic Irradiation with or without Concurrent Weekly Cisplatin in patients with pelvic-only recurrence of carcinoma of the uterine corpus. 22/164 Interested groups: RTOG, NCRI, SWOG GOG-0242 A phase II study to determine the response to Second Currettage as Initial Management of persistent, low risk, non metastatic GTN: 28/66

Endometrial Cancer Commitee Agenda Chicago June 3, 2010 UPDATE ON ACTIVE STUDIES: GOG GOG-0248 A randomized phase II trial of Temsirolimus or the combination of Hormonal Therapy plus Temsirolimus in women with advanced or recurrent endometrial carcinoma: 43/84 GOG-0249 A phase III trial of pelvic RT vs Vaginal Cuff Brachitherapy followed by Paclitaxel-Carboplatin Chemotherapy in patients with high risk, early stage endometrial cancer: 112/562 Intersted group: RTOG

Endometrial Cancer Commitee Agenda Chicago June 3, 2010 UPDATE ON ACTIVE STUDIES: GOG GOG-0258 A randomized phase III trial of Cisplatin and Tumor Directed RT followed by Carboplatin/Paclitaxel vs Carboplatin/Paclitaxel for optimally debulked advanced endometrial cancer: 67/804. Interested group: RTOG GOG-0261 A randomized phase III trial of Carboplatin-Paclitaxel vs Ifosfamide-Paclitaxel in chemotherapy naive patients with newly diagnosed stage I-IV, persistent or recurrent uterine MMT: 47/424. Interested groups: NCRI, GINECO, JGOG, RTOG

Endometrial Cancer Commitee Agenda Chicago June 3, 2010 UPDATE ON ACTIVE STUDIES: NCIC CTG NCIC CTG IND 192 Ridaforolimus in treating patients with recurrent metastatic and/or locally advanced endometrial cancer: 29/32 NCIC CTG IND 179 Phase I of Temsirolimus, Paclitaxel and Carboplatin; have an expanded cohort in endometrial cancer that will continue: completed

Endometrial Cancer Commitee Agenda Chicago June 3, 2010 UPDATE ON ACTIVE STUDIES: DGOG PORTEC 3 Randomized phase III trail comparing Concurrent Chemoradiation and Adjuvant Chemotherapy with palvic Radiation Alone in High Risk and Advanced Endometrial Carcinoma Participating groups: NCRI MaNGO, ANZGOG, NCIC-CTG. NSGO interestd. AFTER 4 A phase III intergroup trial of adjuvant therapy in radically operated endometrial cancer patients with high risk for micro-metastatic disease: 4 courses of adjuvant CT followed by RT versus 2 more courses of CT: Nothing to report