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GCIG reviews: Delineated Process
Consensus review
elaboration by coordinator/co
coordinators N = 20
Review by all members of the RTWG
N = 19
Review by chairs and co chairs from sub committees & from some other groups such as ISTDD or WSN
N = 19
Editing committee
N = 20
Review by all national groups N = 20
Editing board Liverpool 10/2013 N = 20
Group Représentatives: ACRIN S Lee , AGO Au C Marth, AGO De J Pfisterer >, ANZGOG A Brand , COGI J Berek , DGOG C Creutzberg EORTC A Casado, GEICO A Poveda, GICOM D Gallardo, GINECO AC Hardy , GOG T Thigpen , GOTIC K Fujiwara , ICORG D Donnell , JGOG D Aoki , KGOG JW Kim , MaNGO R Fossati , MITO S Pignata , MRC-NCRI J Ledermann , NCIC CTG M Fung-Kee-Fung , NSGO M Mirza , RTOG D Gaffney , SGCTG N Siddiqui , SGOG R Zang , NOGGO J Sehouli , PMHC A Oza
J Bryce, M Friedlander, J Ledermann, A Oza, I Ray-Coquard
Cervix: S Sagae & B Monk Endometrial : K Lorusso & S Greggi Ovarian : P Harter & A Gonzalez
NCI US B Greer; NCI US T Trimble; AGO-De P Harter; ANZGOG M Friedlander; MRC-NCRI C Gourley; GICOM EM Gomez Garcia; MRC-NCRI A Clamp; MRC-NCRI I McNeish; ANZGOG D Rischin; MITO K Lorusso; G Daniele; H Hal; Blagden, SP; NSGO E Avall-Lundqvist; GINECO I Ray-Coquard, SGCTG R Glasspool; ANZGOG C Lee; C Scott; JGOG D Aoki; JGOG group; SWOG M Bookman; NSGO G Kristensen; EORTC N Ottevanger; JGOG N Susumu; G Keiichi
J.Brown, P.Pautier, M.Hensley, F.Amant, M.Leitao, B.Rigaud, X.Cheng, N.Reed, P.Harter, D.Gershenson, C.Gourley, N.Colombo, R.Glasspool, A.Gonzalez, K.Fujiwara, E.Gomez, A.Okamoto, K.Lorusso, Susumu for S.Sagae, A.Viswanathan, M.Seckl, and M.Friedlander,J Lederman, E Pujade- Lauraine, I Ray-Coquard, J Bryce
GCIG consensus reviews update
GCIG consensus review leader Group Coordinator
Co Coordinator step
Ov & Ut carcinosarcoma GINECO D Berton Rigaud Accepted with minor Changes low malignant potential tumors AGO P Harter Submitted low grade serous carcinoma GOG D Gershenson C Gourley Submitted Sex cord tumor GINECO I Ray Coquard N Colombo Submitted germ Cell Tumor GOG J Brown M Seckl Submitted squamous Ov carcinoma SGCTG R Glasspool Antonio Gonzales Submitted Small Cell carcinoma cervix GOTIC K Fujiwara N Reed Accepted with some comments
small cell carcinoma OV EORTC N Reed P Pautier Submitted
vulvar & vagina melanoma US NCI M Leitao Xi Cheng Accepted ovarian carcinoid tumor GICOM N Reed E Gomez Submitted Mucinuous carcinoma MRC/NCRI J Ledermann J Brown Submitted clear cell carcinoma Ovary JGOG A Okamoto R Glasspool Just submitted clear cell carcinoma Cervix & Ut GOTIC K Fujiwara & Dr Hasegawa Need to be submitted trophoblastic diseases MITO K Larusso M Seckl Submitted
low grade endometrial stromal sarcoma EORTC F Amant Submitted
HG uterine sarcoma GINECO P Pautier Submitted uterine serous carcinoma JGOG S Sagae A Viswanathan Need to be submitted
adenosarcoma ANZGOG M Friedlander Accepted with minor changes
Ut & Ov leiomyosarcoma US NCI M Hensley Submitted glandular carcinoma of cervix GOTIC K Fujiwara B Monk Submitted
Next steps for consensus reviews documents
Publications : Publications on website and in journal
One paper summarizing all documents (non answered questions) in progress 20 papers in a supplement (Int J Gyn Cancer) to be finalized
What place for rare tumors in the 5th OCCC, Japan 2015? A special team will be designed to help the Chairs
The most easy part of the job is made, the next will be really more difficult (updating, implementation …) Updating:
Every 3 years for paper version Every year for website version (addendum will be posted if needed) Current coordonator will be asked to be the sentinel for the next 3 years
Implementation within national group: Experiences will be reported next meeting
Objectives: To define current recommendations for rare gynecologic
tumors; To help to define control arm for present and future
clinical trials involving rare cancer; To identify national & international barriers for
trials dedicated to rare gynecologic cancers To summarize and prioritize key issues for
research and agree new set of trial concepts to address the key issues in several rare tumors
To prioritize and design 3 international initiatives in rare gynecologic cancer
GCIG RTWG meeting London Nov. 2013, first step
GCIG Rare Tumors project, the future Publications:
one paper to summarize London meeting (500 words per section) harmonization, statistical, biology and specific recommendations for very very rare, rare and not so rare disease (cut-off date Sept 2014)
More dedicated projects to rare gynecologic cancer
= Limited resources imply concerted actions
Combination of clinical trials and other projects (specific databases & tumor collections)
Next tasks to be delivered: Cervix proposals will be sent to Cervix subgroups for considerations Carcinosarcoma is on –going to be delineated with Phase II group New Proposals adapted to rare diseases/situations A specifc session is anticipated bringing pathologists & clinicians to delineate
recommendations for inclusion of patients in clinical trials with rare tumors (ESGO 2015)
7
ALIENOR DESIGN : 60 patients
Bevacizumab 15mg/Kg every 3 weeks
Paclitaxel alone
80mg/m², IV, at D1, D8 and D15
every 4 weeks
Paclitaxel 80mg/m², IV, D1, D8 and D15
every 4 weeks +
Bevacizumab 10mg/kg, IV, D1 and D15
RANDOMISATION
Maximum of 6 cycles Up to 1 year or until PD / intolerance
Arm A
Arm B
Standard
surveillance
Standard of care
PD or Toxicity
Bevacizumab 15mg/Kg every 3 weeks
Standard of care
PD or Toxicity
At the investigator discretion
Population : Patients with an histologically confirmed diagnosis of ovarian sex-cord stromal tumor in relapse after a platinum-based chemotherapy.
Primary objective : Clinical benefit rate (non-progression rate after 6 months of treatment)
Stratification Anterior chemotherapy lines : 1 or 2 vs 3 and more Platinum Free Interval Interval (PFI) <12 months vs >12 months
ALIENOR - Satellite Meeting
8
20
0
10
20
30
40
50
60
70
Planned
Actual
GINECO First Patient In 28/02/2013
AGO 04/04/2014
• Enrollment period : 36 months First Patient In : February 2013 • Treatment + maintenance : 18 months Last Patient Out of Maintenance : August 2017 • Follow-up : 36 months Last Patient Out : August 2020
ALIENOR - Satellite Meeting
More details during the satellite meeting (13:30 to 14:00)
A Randomised Phase II Study of BIBF 1120 versus Chemotherapy in Recurrent Clear Cell Carcinoma of the
Ovary or Endometrium
SGCTG/NCRI/NSGO
NiCCC Nintedanib in Clear Cell Carcinoma
NiCCC Trial Design
90 pts with progressive or relapsed CCC of ovary within 6 months of previous platinum.
Plus up to 30 women with endometrial CCC
RANDOMISE
Chemotherapy Ovary:
•PLDH (40mg/m2 day 1q28) •Weekly Paclitaxel (80mg/m2 day 1, 8, 15 q28) •Weekly Topotecan iv (4mg/m2 day 1, 8, 15 q28)
Endometrium: •Carboplatin (AUC 5) /Paclitaxel 175 mg/m2 q21 •Doxorubicin 60mg/m2 q21
Nintedanib 200mg bd until progression
Primary Endpoint: PFS
Secondary Endpoints: OS, Toxicity, RR, QoL, Q-Twist
SOON OPEN FOR INCLUSION AUGUST 2014
11
Hyatt Canberra | 26–29 March 2014
Paragon trial: Phase II study of aromatase inhibitors in women with potentially hormone responsive recurrent/metastatic gynaecological
neoplasms SCREENING
Metastatic or recurrent ER+ve and/or PR+ve gynaecological cancer
Epithelial ovarian cancer
1. Rising CA125 after 1st line therapy (closed to further accrual)
2. Recurrent low grade ovarian cancers
3. Platinum resistant/refractory
Endometrial cancer (closed to further accrual)
Endometrial stromal sarcomas
and other
gynaecological sarcomas
Granulosa cell/sex cord
stromal tumours
Suitable for endocrine therapy
REGISTRATION PROCEDURES Signed informed consent
TREATMENT Anastrozole (1 mg daily)
Study visits monthly for first 3 months then every 3 months Tumour markers at each visit (if initially elevated) & imaging every 3 months in
patients with measurable disease
GCIG Meeting, Chicago, May 2014
• There are currently 23 sites recruiting across Australia & New Zealand (ANZGOG) with a further 21 in the United Kingdom (CRUK)
• Current accrual 255 from a target of 350 • Of the seven tumour subgroups, the Epithelial Ovarian cancer - Platinum
Resistant / Refractory and Endometrial subgroups have completed accrual • All other tumour subgroups remain open to recruitment. • Accrual expected to close Dec 2015
GOG 0281/LOGS Trial
• Phase II/III • International trial: UK (NCRI) and US (NRG) • Target sample size = 250 pts • Activated in US 2-14 • Crossover design
R
LOGS Study Trial Schema
Arm A = Control Arm Investigators Choice of following:
• Letrozole 2.5 mg po qd continuously • Tamoxifen 20 mg po bid continuously • Paclitaxel 80 mg/m2 IV over 1 hr on day
1 q. 7d, 3 wks on, 1 wk off • Pegylated Liposomal Doxorubicin 40 or
50 mg/m2 IV over 1 hr on day 1 q. 28d • Topotecan 4.0 mg/m2 over 30 min on
days 1, 8 and 15 of a 28 day cycle For each arm, 1 cycle = 28 days
Arm B = Experimental Arm Trametinib 2 mg po daily
continuous treatment For each arm, 1 cycle = 28 days
Crossover to Trametinib
N = 250 patients Primary endpoint: PFS Secondary endpoints: • Adverse effects • Objective response • Overall survival • Molecular analyses • Quality of Life
Assessments
Clinical: • At screening day 1 of each
cycle • Following disease
progression, pts will be followed every 12 wk
CT Scans: Screening, then every 8 wk until disease progression
Progression
Off Study
Competitive trials on-going:
- MILO trial
- Merck trial (Mek inhibitor plus or less PI3k inh)
The RTWG highlighted how important and constructive could be to have
an academic steering committee across the 3 RCT to support and help
the development of these new drugs for a so small pop of patients
Late Phase II study
1° endpoint: PFS rate at 4 months from randomization 2° endpoints: PFS, OS, RR and duration of response (RECIST 1.1), QoL (QLQ-C30 + QLQ-EN24), Toxicity (CTCAE 4.0)
Locally advanced:
Newly diagnosed HGUS with advanced disease (stage III or stage IV) or residual
disease after primary surgery
Metastatic:
Diagnosed HGUS with disease relapse after local treatment for
primary tumor
Doxorubicin based regimens
4 to 6 cycles of doxorubicin alone or in combination with ifosfamide (for recommended regimens, appendix H)
Screening phase
Cabozantinib maintenance
60 mg QD continuously
2 year or withdrawal criterion
Placebo
2 year or withdrawal criterion
Protocol treatment
Investigator choice
Investigator choice (cabozantinib
allowed)
REGISTRATION
(78 patients expected)
RANDOMIZATION 1:1
(54 patients)
Non-PD within 12 weeks after CT
A randomized double-blind phase II study evaluating the role of maintenance therapy with Cabozantinib in High Grade Uterine Sarcoma (HGUS) after chemotherapy for
advanced or metastatic disease or in metastatic first line treatment
EORTC-CRUK-NCI study in uterine sarcoma
• International Rare Cancer Initiative (IRCI) launched in 2011 to perform clinical trials in different rare tumors. One working group will launch trials.
• Three (sub)studies in the domain of gynaecological sarcoma have been identified: • ESS: Advanced recurrent stage (EORTC lead) – 55112-62111 • HGUS (EORTC lead) – 62113-55115 • Adjuvant treatment of uterine LMS (NCI lead) – 55116-62114
• Question at the end, IRCI will be able to avoid the complexicity of NCI/US organization?
“MaGIC” Malignant Germ Cell
International Collaboration
David Gershenson A. Lindsay Frazier MD Anderson Dana-Farber Cancer Institute
• The IGCCC (International Germ Cell Consensus Collaboration) “revolutioned” testis cancer. • Universally-accepted risk
stratification allowed for international collaboration and comparison.
• Our goal: Duplicate for pediatric germ cell tumors.
• In 2010, COG signed a Memorandum of Understanding with CCLG in the UK and merged 25 years of clinical trial data resulting in data set of ~ 1000 patients.
History and Purpose of MaGIC
• Pediatric Group • COG • CCLG (UK) • TATA Memorial (Mumbai) • Centro Infantil Boldrini
(Brazil) • 57357 Children’s Cancer
Hospital (Cairo)
Collaboration of Major Pediatric and Adult Clinical Trial Groups
• Gyn Oncology • NRG • ? • Testis Cancer • Alliance • SWOG • ECOG • MRC (UK) • ANZUP (Australia/NZ)
• Goals and Specific Aims
1. Eliminate chemotherapy for all Stage I patients • All stage I ovarian germ cell tumors will be observed after surgery
• Stratum 1: Stage I pure immature teratoma, all grades • Stratum 2: MGCT that contain at least one of the following:
Yolk sac tumor, embyronal carcinoma or choriocarcinoma.
2. Evaluate carboplatin vs. cisplatin • Expect to accrue 588 patients over 6 years
• Have 88% power to detect carboplatin as inferior if the long term EFS for BEP is 84% and EFS for JEB is 76%
• (Relative hazard ratio of 1.6)
Children’s Oncology Group AGCT1431
• Poor risk “Germinational” Trial • Will require cooperation of pediatric, gynecologic oncology
and testes cancer groups • Potential regimens: - Dose dense (Accel-BEP every 2 weeks) - New agents (TIP –taxol, ifosfamide, platinum) - Combination of both: GETUG13 or CBOP-BEP
• Optimal therapy for dysgerminoma • Optimal therapy for immature teratoma • Surgical guidelines for germ cell tumors
Other topics under discussion
People from the RT group will be very happy to participate Some concerns about the administrative limits induced by NCI cooperative
group Contacts will be organized
The most « sexy » proposal from GOG
Carcinosarcoma Uterine and Ovarian
SOC: Surgical staging +TC
+/-RT
SOC+ Anti-angiogenic
+/-RT
Recurrence Experimental 1
Experimental 2
Chemotherapy
Molecular Pathology, Staging
Randomization 1 At initial diagnosis Stage and Pathology
Randomization 2 At Recurrence - Stage and Bx
Patients can enroll At Randomization 1 or 2
n= 100s
N=100s
AKT inhibitor
PARP inhibitor
Carboplatin/paclitaxel plus Cedirinib
Clinician choice?
Possibility to add/remove experimental arms
Intergroup agreement AZ seems to be interested People from the RT group will be very happy to participate Consortium will be organized
Umbrella trial delineated during the London Brainstorming meeting
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