Endometrial Committee

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Endometrial Committee

• David Scott Miller, M.D., F.A.C.O.G., F.A.C.S.
• Director and Dallas Foundation Chair in
  Gynecologic Oncology
• Professor of Obstetrics Gynecology
• University of Texas Southwestern Medical Center
• Dallas, Texas, U.S.A.

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Resected Endometrial

• GOG0249 A Phase III Trial of Pelvic Radiation
  Therapy versus Vaginal Cuff Brachytherapy
  Followed by Paclitaxel/Carboplatin Chemotherapy
  in Patients with High Risk, Early Stage
  Endometrial Cancer (23 Mar 2009)
• RTOG

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Resected Endometrial

• PORTEC 3 Randomized Phase III Trial Comparing
  Concurrent Chemoradiation and Adjuvant
  Chemotherapy with Pelvic Radiation Alone in High
  Risk and Advanced Stage Endometrial Carcinoma
• MaNGO, ANZGOG, NRCI, NCIC-CTG, NSGO

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Resected Endometrial

• GOG258 (UC0704) A Randomized Phase III Trial of
  Cisplatin and Tumor Volume Directed Irradiation
  Followed by Carboplatin and Paclitaxel vs.
  Carboplatin and Paclitaxel for Optimally
  Debulked, Advanced Endometrial Cancer (29 Jun
  2009)
• RTOG

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Results of previous studies
Study proposal
Pooled survival data
NSGO
The combination of RT CT is better than RT
Proposed new study exploring if the combination
of RT and CT is superior to CT After 4 - A Phase
III intergroup trial on adjuvant therapy in
radically operated endometrial cancer patients
(FIGO stage IC-IIIC) with high risk for
micrometastatic disease
Thomas Hogberg, Lund Univ Hosp Oct 2009
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PORTEC-3 Unless there is something fundamentally
wrong with NSGO-9501/EORTC-55991 PORTEC-3 will
most probably show that CMT is better than RT
The question about the contribution of RT will
remain unanswered
When PORTEC-3 is published CMT will probably
become standard treatment
We have a time-frame in which we can resolve
the question of the value of addition of
radiotherapy to chemotherapy
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Proposed study
RT
Randomization
N1000
Radical surgery TAHBSOLA CTx4
CTx2
Main inclusion criteria a. Endometrioid
carcinoma b. Stage 1C grade 3 c. Stage IIA grade
3 and MI50, IIB d. Stage IIIA-C Radical
surgery, LA recommended but optional Main
exclusion criteria Serous or clear cell
carcinoma IIIA with only pos fluid cytology
CT Paclitaxel 175 mg/m2, carboplatin AUC 5-6
(calculated) q 3 weeks
Primary endpoint Overall survival (OS)
Thomas Hogberg, Lund Univ Hosp Oct 2009
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Pelvic Recurrence

• GOG0238 A Randomized Trial of Pelvic Irradiation
  with or without Concurrent Weekly Cisplatin in
  Patients with Pelvic-only Recurrence of Carcinoma
  of the Uterine Corpus
• RTOG, NCRI, SWOG

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Advanced/Recurrent

• NCIC EN 8 Randomized Phase III Study of
  progestational hormone therapy versus deforolimus
  in women with recurrent or metastatic endometrial
  cancer
• ACRIN, AGO-AUST, AGO-OVAR, ANZOG, EORTC, GEICO,
  GINECO, JGOG, MANGO, MITO, NCRI, NSGO, SWOG

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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,
ANZGOG?, DUTCH GOG, EORTC, GEICO, GINECO, JGOG,
MANGO, MITO, NCRI, NSGO, SWOG
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Proposed Design Change

• Accrual to the phase 2 studies has been slower
  than expected.  
• Reasons start up for centres, increasing use of
  prior chemotherapy in preference to hormonal
  agent.  
• Consider allowing either hormonal OR chemotherapy
  as the control arm for this study.

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

• GOG0261 Randomized Phase III Trial of
  Carboplatin plus Paclitaxel versus Ifosfamide
  plus Taxol in Patients with Advanced, Persistent
  or Recurrent Carcinosarcoma
• NCRI, GINECO, JGOG, RTOG

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Leiomyosarcoma

• GOG0250 Randomized Phase III Evaluation of
  Docetaxel, Gemcitabine, G-CSF /- Bevacizumab
  in the Treatment of Recurrent or Advanced
  Leiomyosarcoma

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GTN

• Charge from the Executive
• RFP
• ISSTD

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GTD Concepts

• Hydatidiform Mole Registry (Quinn)
• Pulse Act-D vs. 8 day MTX for Low Risk GTN