Download Current and Future Clinical Trials

Current and Future Clinical Trials
Andreas Obermair
Pathways
Evidence (Mirena)
Prevention of progression
Oral Progestin vs. IUD
Progestins offered on case-to-case basis
(Mirena ± oral progestins)
Baker et al.: Gynecologic Oncology Volume 125, Issue 1 2012 263 - 270
Pathological complete response to oral and
IUD-delivered progestin treatment
Abbreviations: CAH, complex atypical endometrial hyperplasia; EC, endometrioid adenocarcinoma
Baker et al.: Gynecologic Oncology Volume 125, Issue 1 2012 263 - 270
Metaanalysis of relapse rates for fertilitysparing treatment of endometrial cancer
40%
Ioannis D. Gallos et al.: American Journal of Obstetrics and Gynecology Volume 207, Issue 4 2012 266.e1 - 266.e12
Metaanalysis of live birth rates for fertilitysparing treatment of endometrial cancer
30%
Ioannis D. Gallos et al.: American Journal of Obstetrics and Gynecology Volume 207, Issue 4 2012 266.e1 - 266.e12
Ongoing Trials
Chemoprevention with Metformin
 Randomized, 4-arm study, placebo-controlled (double blind)
 Include: Postmenopausal, obese women (BMI > 35 [who are at
risk to develop endometrial cancer])
 Intervention: Metformin (850 mg bd for 4 months), Lifestyle
intervention (weight loss, supervised exercise)
 Outcome: Effect of Metformin & Lifestyle intervention on
biomarkers associated with endometrial proliferation
 Commenced March 2013 (2019)
 N = 100
 Contact: Karen Lu, MD Anderson, TX
Mirena + MPA
 Single-arm, prospective, multi-institutional study
 Include: EAC, g1, confined to endometrium*; wishing to
maintain fertility (< 40 years)
 Intervention: Mirena + MPA (500 mg/d); 3-monthly endometrial
samplings
 Outcome: Pathological response rate at 24 months
 Commenced January 2012 (2 years)
 N= 39
 Contact: Korean GOG
*Assessment method not defined
Mirena
 Single-arm, prospective, multi-institutional study
 Include: endometrial hyperplasia* who wish to maintain fertility
(>20 years)
 Intervention: Mirena IUD; endometrial sampling + TVUS every 3
months
 Outcome: Pathological response rate at 12 months
 Commenced November 2010 (2 years)
 N= 80
 Contact: Korean GOG
*Simple :: Complex :: Atypical not defined
Megestrol (Hyperplasia only)
 Three-arm, prospective, multi-institutional study
 Include: atypical endometrial hyperplasia/EIN; must agree to a
hysterectomy
 Exclude: Endometrial cancer
 Intervention: Megestrol in different doses and sequence (4 arms),
placebo-controlled
 Outcomes: Response rate at 24 weeks
 Commenced July 2007
 N= 260
 Contact: US GOG
feMME (AUS)
 Three-arm, prospective, multi-institutional study
 Include: atypical endometrial hyperplasia or EAC g1, CA125 <
30 U/ml, myoinvasion < 50% (MRI)
 Intervention: Mirena vs. Mirena + Metformin vs. Mirena +
lifestyle intervention (weight loss, exercise)
 Outcomes: Response rate at 6 months
 Commence: July 2013
 N= 165
 Contact: QLD Centre for Gynaecological Cancer
Summary of Treatment Trials
Mirena + MPA
(Korea)
Mirena
(Korea)
Megestrol
(GOG)
feMME
(AUS)
Indication
EHA, EAC
EHA, EAC
EHA
EHA, EAC
Allocation
Single-arm
Single-arm
3 arm
3 arm
Mirena + MPA
Mirena IUD
Megestrol
acetate
Mirena,
Metformin,
Life style
intervention
Response at
24/12
Response at
12/12
Response at
24/52
Response at
6/12
2012
2010
2007
2013
39
80
260
165
Intervention
Outcome
Year
N
Evidence (weight loss)
 Weight loss is feasible (7%)
 V van Grueningen et al: Gynecol Oncol 2012
 Preoperative weight loss: 7% achievable
 Prostate cancer response through lifestyle intervention
(diet + weight loss)
Evidence (Metformin)
Anti-diabetic drug
 In-vitro
 Pharmaco-epidemiological data
 Case-reports
Evidence – Metformin
Gentler and kinder way to treat
Patients with Endometrial Cancer
Morbidly obese
woman > 130 kg;
EAC FIGO g1, no
myoinvasion
Day 5: Respiratory
failure secondary to
pneumonia
Unplanned ICU
admission;
Requires ventilation,
imaging, i.v. ABs
Kondalsamy-Chennakesavan S et al: Eur J Cancer. 2012 Sep;48(14):2155-62
Schema: Mirena ± Metformin ± Weight Loss
 Primary: Pathological Complete Response at 6 months
 Secondary: To predict the response to treatment through
clinical, blood and tissue molecular biomarkers and to
increase our molecular understanding of the biological
pathogenesis of “early” EAC.
feMME Trial - Eligibility
Target: 165 patients with complex endometrial hyperplasia with
atypia or grade 1 EAC
Eligibility:
 Complex Endometrial Hyperplasia with atypia OR
 Grade 1 EAC – avoid enrolling patients with advanced disease
who need expedited surgery
 Patients at high surgical risks or wish to retain fertility
 BMI > 30 kg/m2
 CT scan: absence of extrauterine disease
 Myometrial invasion <50% (MRI)
 Serum CA125 ≤30 U/mL
Contact
QLD Centre for Gynaecological Cancer
Andreas Obermair: [email protected]
Acknowledgements: M Janda (QUT), ANZGOG (RAC), Val Gebski (CTC)
Endorsed jointly by ANZGOG and ASGO
National Ethics Application (covers NSW, VIC)
QCGC will assist with HREC applications.