Rare Tumors Presentation

GCIG reviews: Delineated Process
Consensus
review
elaboration by
coordinator/co
coordinators
N = 20
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 PujadeLauraine, I Ray-Coquard, J Bryce
Editing board
Liverpool
10/2013
N = 20
Group Représentatives: ACRIN S Lee ,
AGO Au C Marth, AGO De J Pfisterer >,
Review by all
ANZGOG A Brand , COGI J Berek ,
DGOG C Creutzberg EORTC A Casado, national
groups
GEICO A Poveda, GICOM D Gallardo,
N = 20
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-KeeFung , NSGO M Mirza , RTOG D Gaffney
, SGCTG N Siddiqui , SGOG R Zang ,
NOGGO J Sehouli , PMHC A Oza
Review by all
members of
the RTWG
N = 19
NCI US B Greer; NCI US T Trimble; AGODe 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 RayCoquard, 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
Review by chairs
and co chairs from
sub committees &
from some other
groups such as
ISTDD or WSN
N = 19
Editing
committee
N = 20
Cervix: S Sagae & B Monk
Endometrial : K Lorusso & S Greggi
Ovarian : P Harter & A Gonzalez
J Bryce, M Friedlander, J Ledermann, A Oza, I Ray-Coquard
GCIG consensus reviews update
GCIG consensus review
leader
Group
Co
Coordinator Coordinator
Ov& Ut carcinosarcoma
GINECO
DBerton Rigaud
AcceptedwithminorChanges
lowmalignant potential tumors
AGO
PHarter
Submitted
lowgradeserouscarcinoma
GOG
DGershenson
CGourley
Submitted
Sexcord tumor
GINECO
IRayCoquard
NColombo
Submitted
germCell Tumor
GOG
JBrown
MSeckl
Submitted
squamousOvcarcinoma
SGCTG
RGlasspool
Antonio Gonzales Submitted
Small Cell carcinoma cervix
GOTIC
KFujiwara
NReed
Accepted with somecomments
smallcell carcinoma OV
EORTC
NReed
PPautier
Submitted
vulvar &vagina melanoma
USNCI
MLeitao
XiCheng
Accepted
ovarian carcinoid tumor
GICOM
NReed
EGomez
Submitted
Mucinuous carcinoma
MRC/NCRI
JLedermann
JBrown
Submitted
clearcell carcinoma Ovary
JGOG
AOkamoto
RGlasspool
Justsubmitted
clearcell carcinoma Cervix & Ut
GOTIC
KFujiwara & DrHasegawa
Needtobesubmitted
trophoblastic diseases
MITO
KLarusso
Submitted
lowgradeendometrial stromal sarcoma
EORTC
FAmant
Submitted
HGuterine sarcoma
GINECO
PPautier
Submitted
uterine serouscarcinoma
JGOG
SSagae
adenosarcoma
ANZGOG
MFriedlander
Accepted with minor changes
Ut &Ov leiomyosarcoma
USNCI
MHensley
Submitted
glandular carcinoma ofcervix
GOTIC
KFujiwara
MSeckl
AViswanathan
BMonk
step
Needtobesubmitted
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
GCIG RTWG meeting
London Nov. 2013, first step
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 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)

ALIENOR DESIGN : 60 patients
R
A
N
D
O
M
I
S
A
T
I
O
N
Arm A
Paclitaxel alone
80mg/m², IV, at D1, D8 and D15
every 4 weeks
Standard
surveillance
PD or
Toxicity
Standard
of care
Bevacizumab
15mg/Kg every 3 weeks
At the investigator discretion
Paclitaxel
Arm B
80mg/m², IV, D1, D8 and D15
every 4 weeks
+
Bevacizumab
PD or
Toxicity
15mg/Kg every 3 weeks
Bevacizumab
Standard
of care
10mg/kg, IV, D1 and D15
Maximum of 6 cycles
Population :
Patients with an histologically
confirmed diagnosis of
ovarian sex-cord stromal
tumor in relapse after a
platinum-based
chemotherapy.
7
Up to 1 year or until PD /
intolerance
Primary objective :
Clinical benefit rate
(non-progression rate after
6 months of treatment)
ALIENOR - Satellite Meeting
Stratification
Anterior chemotherapy lines :
1 or 2 vs 3 and more
Platinum Free Interval Interval (PFI)
<12 months vs >12 months
More details during the satellite meeting (13:30 to 14:00)
70
60
50
40
AGO
04/04/2014
30
20 GINECO
10
20
Planned
Actual
First Patient In
28/02/2013
0
• Enrollment period : 36 months
• Treatment + maintenance : 18 months
• Follow-up : 36 months
8
ALIENOR - Satellite Meeting
First Patient In : February 2013
Last Patient Out of Maintenance : August 2017
Last Patient Out : August 2020
NiCCC
Nintedanib in Clear Cell Carcinoma
A Randomised Phase II Study of BIBF 1120 versus
Chemotherapy in Recurrent Clear Cell Carcinoma of the
Ovary or Endometrium
SGCTG/NCRI/NSGO
NiCCC Trial Design
Chemotherapy
Ovary:
90 pts with
progressive or
relapsed CCC of
ovary within 6
months of
previous platinum.
Plus up to 30
women with
endometrial CCC
R
A
N
D
O
M
I
S
E
•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
Paragon trial: Phase II study of aromatase inhibitors in women with 11
potentially hormone responsive recurrent/metastatic gynaecological
neoplasms
SCREENING
Metastatic or recurrent ER+ve and/or PR+ve gynaecological cancer
Endometrial
Granulosa
Endometrial
Epithelial ovarian cancer
stromal sarcomas
cell/sex cord
cancer
1. Rising CA125 after 1st line
stromal tumours
(closed to
therapy (closed to further
and other
further accrual)
accrual)
gynaecological
Suitable for
2. Recurrent low grade ovarian
• cancers
There are currently 23 sites recruiting across Australia
&
New
Zealand
sarcomas
endocrine therapy
3. Platinum
resistant/refractory
(ANZGOG)
with a further 21 in the United Kingdom (CRUK)
• Current accrual 255 from a target of 350
REGISTRATION PROCEDURES
• Of the seven tumour subgroups,
Epithelial
Signedthe
informed
consent Ovarian cancer - Platinum
Resistant / Refractory and Endometrial subgroups have completed accrual
TREATMENT
• All other tumour subgroups remain
open to recruitment.
Anastrozole (1 mg daily)
• Accrual expected
to
close
Dec
2015
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,
Hyatt
Canberra
| 26–29 May
March2014
2014
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
Assessments
N = 250 patients
Primary endpoint: PFS
Secondary endpoints:
•
Adverse effects
•
Objective response
•
Overall survival
•
Molecular analyses
•
Quality of Life
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, 3trials
wks on,on-going:
1 wk off
Competitive
• Pegylated Liposomal Doxorubicin 40 or
mg/m2 IV over 1 hr on day 1 q. 28d
- MILO50trial
• Topotecan 4.0 mg/m2 over 30 min on
days
1, 8 and
15 ofinhibitor
a 28 day cycle
- Merck
trial
(Mek
plus or
For each arm, 1 cycle = 28 days
R
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
Arm B = Experimental Arm
Trametinib 2 mg po daily
continuous treatment
For each arm, 1 cycle = 28 days
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
Progression
the development of these new drugs
for a so small pop of patients
Crossover to Trametinib
Off Study
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
RANDOMIZATION 1:1
REGISTRATION
(78 patients expected)
(54 patients)
Late Phase II study
Non-PD within 12 weeks after CT
Cabozantinib maintenance
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
60 mg QD continuously
Investigator choice
2 year or withdrawal criterion
Doxorubicin based regimens
4 to 6 cycles of doxorubicin alone or
in combination with ifosfamide (for
recommended regimens, appendix
H)
Protocol treatment
Placebo
Screening phase
2 year or withdrawal
criterion
Investigator choice
(cabozantinib
allowed)
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)
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
MD Anderson
A. Lindsay Frazier
Dana-Farber Cancer Institute
History and Purpose of MaGIC
• 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.
Collaboration of Major Pediatric
and Adult Clinical Trial Groups
• Pediatric Group
• Gyn Oncology
• COG
• NRG
• CCLG (UK)
• ?
• TATA Memorial (Mumbai)
• Testis Cancer
• Centro Infantil Boldrini
(Brazil)
• Alliance
• 57357 Children’s Cancer
Hospital (Cairo)
• ECOG
• SWOG
• MRC (UK)
• ANZUP (Australia/NZ)
Children’s Oncology Group
AGCT1431
• 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)
Other topics under discussion
• 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
(TIP
ifosfamide,
platinum)
 People from- the
RTagents
group will
be–taxol,
very happy
to participate
 Some concerns
about the administrative
limits induced
by NCI cooperative
- Combination
of both: GETUG13
or CBOP-BEP
group
• Optimal
therapy for dysgerminoma
 Contacts
will be organized
• Optimal therapy for immature teratoma
• Surgical guidelines for germ cell tumors
The most « sexy » proposal from GOG
Umbrella trial delineated during the London Brainstorming meeting
Patients can enroll
At Randomization
1 or 2
Carcinosarcoma
Uterine and Ovarian
Randomization 1
At initial diagnosis
Stage and Pathology
Molecular
Pathology, Staging
SOC+
SOC: Surgical
staging +TC
+/-RT
Anti-angiogenic
+/-RT
Recurrence




Carboplatin/paclitaxel
plus Cedirinib
Possibility to add/remove
experimental arms
Experimental 1
Randomization 2
Intergroup agreement
Experimental 2
AZ seems toAtbeRecurrence
interestedand
Bx will be very happy to participate
People fromStage
the RT
group
Consortium will be organized
N=100s
n= 100s
Chemotherapy
AKT inhibitor
PARP
inhibitor
Clinician
choice?