GCIG Endometrial Cancer Committee Chair: Stefano Greggi Co-chair: Carien Creutzberg AGENDA Welcome – COI - Introductions 1. 2. Approval of minutes of October 2016 meeting 3. Closed trials 4. Ongoing trials 5. Activating trials 6. New trial proposals 7. Challenging Debate: • First line chemotherapy vs. molecular genetics based treatment for recurrent/metastatic EC • Gini Fleming vs Karen Lu 8. Discussion
GCIG Endometrial Cancer Committee Chair: Stefano Greggi Co-chair: Carien Creutzberg GCIG Trial Presentation Guidelines (2017): 1. Closed trials (Site Committee Chair): o Lead group should prepare 1 slide using the attached template. o NEWLY closed trials since the last meeting – final accrual o PREVIOUSLY closed trials – presentation plan, publications and plans 2. Ongoing trials without substantial NEW information (Site Committee Chair): o Lead group should prepare 2 slides using the attached template 3. Ongoing trials with substantial NEW information: o Lead group to request a time slot of 5 minutes and prepare up to 5 slides. Trial slides will be presented by lead group representative o Trials presented at the last GCIG meeting as “NEW TRIALS” are considered as ongoing 4. New trial concepts: o Concept/trial design presentation – lead group to request a time slot of 5 minutes o Trial proposal (funded/recruiting member participation) – lead group to request a time slot of up 15 minutes (10 for presentation and 5 for discussion/questions)
GCIG Endometrial Cancer Committee Chair: Stefano Greggi Co-chair: Carien Creutzberg Closed trials
Closed Trial – status update PORTEC-3 trial / EN7 Trial setting: High-risk endometrial cancer (stages IB-III) Study Design: Randomised trial of RT alone vs RT plus chemotherapy Sponsor(s): LUMC – Funding: Dutch Cancer Society; CRUK; NHMRC; IMA; CCTG Final No. of patients: 686 (660 evaluable) Timeline (first patient – trial closing): 2006-2013 Publications: Toxicity and QoL: de Boer et al, Lancet Oncology 2016 Side studies: Patient preferences: Blinman et al, BJC 2016; QA ANZGOG: Jameson et al, J Med Imaging Radiat Oncol 2016 Planned publications: Final analysis; Pathology review Planned further studies: TransPORTEC analyses
GOG 249 Endometrial cancer: Stage I/II Adjuvant • 3/23/2009 – 2/4/2013: Completed • Endorsed by RTOG • 562 accrued, 9% CCOP • Presented: SGO 2014 • Publication: in preparation
GOG 258 Endometrial cancer : Stage III/IV • 6/29/2009 – 7/28/2014: Completed • Endorsed by RTOG • 813/804 accrued • Presentation: ASCO 2017
GOG 277 Leiomyosarcoma: Stage I 4 Jun 2012 opened 38/216 accrued 9 Sep 2016 closed International Rare Cancers Initiative - Gynaecological sarcoma: EORTC
GOG-0275: A PHASE III RANDOMIZED TRIAL OF PULSE ACTINOMYCIN-D VERSUS MULTI-DAY METHOTREXATE FOR THE TREATMENT OF LOW-RISK GESTATIONAL TROPHOBLASTIC NEOPLASIA Study Chair: Julian Schink, MD Arm Regimen 1 : IV actinomycin-D (1.25mg/m 2 ) every 14 days. (2mg max dose) R Eligible A patients: N Arm Regimen 2 : Low-risk D IV methotrexate (0.4 mg/kg) daily for GTN O 5 days every 14 days. (25mg max daily FIGO M dose) Score 0-6 I OR Z IM methotrexate(50mg) on Days 1, 3, 5, 7 E (4 doses per cycle) with Leucovorin (15mg) on Days 2, 4, 6, 8. Repeat every 14 days. Opened June ‘12. 57/381 recruited: closed Sep ‘16
GCIG Endometrial Cancer Committee Chicago, June 2017 Ongoing trials
Ongoing Trials – status update TOTEM Study: Multicentric randomized controlled clinical trial between two follow up regimens with different tests intensity in endometrial cancer treated patients / NCT 00916708 Trial setting : patients surgically treated for endometrial cancer, if in complete clinical remission confirmed by imaging, FIGO stage I-IV Study Design : multicentric RCT between minimalist and intensive follow up (after first stratification of patients between low risk [IA G1- 2] and high risk [≥ IA G3] of recurrence) Primary objective: compare the effect of the two follow-up regimens on 5-years overall survival. Sponsor (s): Azienda Ospedaliera San Giovanni Battista (now: Azienda Ospedaliero- Universitaria Città della Salute e della Scienza di Torino)
Ongoing Trials – status update TOTEM Study: Multicentric randomized controlled clinical trial between two follow up regimens with different tests intensity in endometrial cancer treated patients / NCT 00916708 Planned No. of patients : 2300 Current accrual : 1651 patients enrolled on 10th May 2017 Other important information : 2 French Institutions shared the trial (total number of units sharing the trial: 41) the interim analysis is ongoing: are we able to close the trial?
ENGOT-EN1/FANDANGO A randomised double-blind placebo-controlled phase II trial of first line combination chemo- therapy with nintedanib/placebo for patients with advanced or recurrent endometrial cancer. Randomization 1:1 N = 148 Stratification: Sponsor: NSGO Project Manager: Mette Berensen • Stage of disease (stage 3C 2 vs. stage 4 vs. recurrent disease) Statistitian: René DePont Christensen • Prior adjuvant chemotherapy (yes/no) PI: Mansoor Raza Mirza • Disease status (Measurable vs. non-measurable disease according to RECIST 1.1) Primary Objectives: To compare Progression Free Survival (PFS)
ENGOT-EN1/FANDANGO Inclusion criteria Histological confirmed endometrial cancer. • Stage 3C 2 • Stage 4 A & B • Relapsed after adjuvant therapy for stage 1-3 disease Prior therapy 2. Patients may have undergone primary surgery. 3. Patients may have received adjuvant chemotherapy for stage 1 – 3. 4. Patients may have received vaginal brachytherapy 5. Patients may have received external beam radiotherapy. Patients who are to be enrolled for stage 3C2 diseases are allowed to receive external beam radiotherapy prior to trial entry. 6. Patients may have received hormonal treatment Disease status 7. Patients must have measurable disease or non-measurable disease on CT scan according to RECIST 1.1 outside irradiated field. For stage 3C2 disease patients without measureable or non-measureable disease are accepted.
ENGOT-EN1/FANDANGO Randomized Patients 160 140 120 100 Number of patients 80 60 40 20 0 Nov 16 Dec 16 Jan 17 Feb 17 Mar 17 Apr 17 May 17 Jun 17 Jul 17 Aug 17 Sep 17 Okt 17 Nov 17 Dec 17 Jan 18 Feb 18 Mar 18 Apr 18 May 18 Expected Randomized patients Randomized patients 148 Patients in total
Postoperative chemotherapy or no further treatment for patients with node-negative stage I-II intermediate or high risk endometrial cancer. ENGOT-EN2-DGCG - NCT01244789 1:1 randomization N=240 Chemotherapy Carboplatin-Paclitaxel x 6 Endometrioid: + Brachytherapy Stage I - G3; II Non-endometrioid: Supported by Stage I-II Observation + Brachytherapy Randomized till date = 165/240
ENGOT-EN2-DGCG Study Population 5-yr survival Creasman et al., IJGO, 2007
A randomized phase II trial of Palbociclib in combination with letrozole versus letrozole for patients with oestrogen receptor positive recurrent endometrial cancer . ENGOT-EN3-NSGO/PALEO Cyclin-Dependent Kinase (CDK) Inhibitors - Oncogenesis is dependent upon cell-cycle regulatory process - Cyclins act as activators to cyclin-dependent kinases - Proliferative CDKs 2, 4, 6 regulate the transition from G1 to S phase - In ER+ cell lines, E2F transcription & cell-cycle progression can occur independent of estrogen. These cells rely on CDK4 to activate E2F - CDK4/6 inhibitors are active in ER+ cell-lines - Letrozole & CDK4/6 inhibitor (Palbociclib) are synergistic Weinberg; Science 2014 Roberts et al. JNCI 2012 Schwartz et al. JCO 2005 Miller et al. Cancer Discov 2011
A randomized phase II trial of Palbociclib in combination with letrozole versus letrozole for patients with oestrogen receptor positive recurrent endometrial cancer. ENGOT-EN3-NSGO/PALEO ARM A Randomization: 1:1 Letrozole, 2.5mg d 1-28 every 28 days Endometrial Cancer N=78 Placebo d 1-21 every 28 days Primary stage 4 or Until progression relapsed incurable Randomize disease ARM B ER positive Letrozole, 2.5mg d 1-28 every 28 days endometrioid Palbociclib 125mg d 1-21 every 28 days adenocarcinoma Until progression Stratification: NCT02730429 Number of prior lines of therapy (primary advanced disease vs. 1 st relapse vs. ≥2 • relapses) • Measurable vs. evaluable disease • Prior use of MPA/Megace (prior MPA/Megace use capped to a maximum of 50%) Study Chair: Mirza MR
STATEC/NCRI FIGO Stage I endometrial cancer - FIGO grade 3 endometrioid or mucinous - High grade serous, clear cell, undifferentiated or de-differentiated carcinoma or mixed cell adenocarcinoma or carcinosarcoma RANDOMISE (2000 patients) Sentinel node Hysterectomy and BSO* Hysterectomy and BSO* *Option for patients to be sub study plus lymphadenectomy randomised < 28 days after (pelvic/PA) hysterectomy and BSO Lymph node Lymph node Lymph nodes positive ~ 20% negative ~ 80% unknown Vaginal Systemic adjuvant treatment: brachytherapy chemotherapy +/- pelvic radiotherapy 5-year follow up, including adverse events and quality of life
STATEC/NCRI Sponsor: University College London (UK) 2 UK sites open (April 2017), 20-30 in setup 1 patient recruited at 12 May 2017 ANZGOG to open sites, DGOG in setup
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