Transcript SARC Executive Committee Meeting

SARC020 – EORTC 62091
TRUSTS – A phase IIb/III multicenter study
comparing the efficacy of TRabectedin
administered as a 3-hour or 24-hour
infusion to doxorubicin in patients with
advanced or metastatic Untreated Soft
Tissue Sarcoma
Study PI: James Butrynski, MD
Dana Farber Cancer Institute/SARC
Binh Bui, MD
Institut Bergonie/EORTC
Primary Objective
To determine whether trabectedin given
as 1st line chemotherapy for
advanced/metastatic soft tissue sarcoma
prolongs progression free survival, as
compared to doxorubicin.
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Secondary End Points
• Overall survival
• Response rate and response duration
• Quality of Life
• Adverse Events/Safety Profile
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Study
design
Randomized phase II b / III trial
Inclusion Criteria
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Histologically proven advanced and/or metastatic malignant soft
tissue sarcoma of intermediate/high grade not previously treated
(see protocol Appendix B)
 Excluded: WD liposarcoma, embryonal rhabdomyosarcoma,
Ewing’s, GIST, DFSP
Paraffin blocks or representative H/E slides must be available for
histological central review
Confirmed disease progression – investigator judgment
Presence of measureable disease according to RECIST 1.1
No anti-cancer therapy or other investigational agents within 28 days
prior to treatment start
Adequate organ function as defined by protocol
WHO performance status 0 or 1
At least 18 years old
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Exclusion Criteria
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History of CNS metastases or leptomeningeal tumor
spread
Prior treatment with anthracyclines for advanced or
metastatic STS
Women who are pregnant or breastfeeding
Active/uncontrolled infections or medical conditions,
including history of chronic alcohol abuse, hepatitis, HIV
and cirrhosis
History within past five years of malignancies other than
STS (see protocol Section 3 Patient Selection Criteria for
exceptions)
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SARC020
Study Status
Total Sites Activated:
US – 7 Sites / 10
EU – 19 Sites / 37 TOTAL : 25/47
Total Patients Enrolled:
US – 21 Patients
EU – 112 Patients
Current Status:
Accrual for Step 1 completed; enrollment
on hold as of 8/6/2012 for interim analysis
SARC020
Participating Centers US
7 Open sites in US:
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Carolina’s Hematology Oncology Associates
Dana-Farber Cancer Institute
Nebraska Methodist Hospital
Pennsylvania Oncology Hematology Associates
Sarcoma Oncology Center
Stanford
University of Iowa
Sites in progress:
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Washington University
University of Pittsburgh
Cedars Sinai
Recruitment / Country
Trabectedin 3 hrs
Trabectedin 24 hrs
Doxo
Total
France
16
14
16
46
The Netherlands
4
3
4
11
U.S.A
2
6
2
10
Germany
3
2
4
9
Austria
2
-
-
2
Spain
1
-
1
2
Total
28
25
27
80
Translational research program
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Predictive value of molecular markers
• Identify / validate biomarkers of sensitivity to trabectedin and
doxorubicin
• Focus on proteins related to the mechanism of action of trabectedin
• DNA repair proteins
• Key genes in the development / prognosis of sarcoma subtypes.
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FFPE or unstained slides from initial diagnosis
• Material collected for the confirmation of diagnosis
• Technique: IHC with guidelines from PharmaMar
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Optional (additional IC required)
• Must be proposed to all patients
Recrutment / Center
227.Centre Léon Bérard (FR)
228.Institut Bergonie (FR)
229.Centre G.F.Leclerc (FR)
234.Centre Oscar Lambret
(FR)
235.Centre R.Gauducheau
(FR)
259.H.Necker-I.Curie (FR)
287.C.H.U. De La Timone
(FR)
301.N.K.I / A.V.L. A'Dam (NL)
302 Erasmus MC R’Dam
(NL)
310 UMC Leiden (NL)
3039.Un.C.G.C. Dresden
(DE)
335.UMCG (NL)
527.Univ. Mannheim (DE)
906. Med Univ. Vienna (AU)
8673.Univ Of Iowa Hosp
(US)
9178.Sarcoma Onco Cter
(US)
9361.Carolinas MC (US)
Total
Trabectedi
n 3 hrs
1
Trabectedin 24 hrs
Doxo
Total
1
1
3
4
5
5
14
3
1
4
8
4
4
4
12
1
-
1
2
2
-
1
3
1
3
-
4
1
1
2
4
1
1
-
2
1
-
-
1
1
1
1
3
1
1
2
4
1
1
1
3
2
-
-
2
1
3
2
6
-
2
-
2
1
1
-
2
28
25
27
80
RECIST 1.1 (1)
Measurable disease:
Presence of at least one measurable
lesion. If the measurable disease is
restricted to a solitary lesion, its
neoplastic nature should be confirmed by
cytology/histology
SARC020
Participating Centers EU
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Austria
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Centre Leon Berard
Centre Georges-Francois-Leclerc
Institut Bergonie
Centre Oscar Lambret
Institut de Cancerologie de l’Ouest (ICO) –
Centre Rene Gauducheau
Institut Curie
Assistance Publique - Hôpitaux de Marseille –
Hôpital de La Timone
Germany
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Universitaetsklinikum Koeln
UniversitaetsMedizin Mannheim
Universitaetsklinikum Carl Gustav Carus
Klinikum Grosshadern Ludwig-Maximilians Univ.
Muenchen
The Netherlands
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Medical University Vienna - General Hospital
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France
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Spain
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Hospital General Vall D'Hebron
Switzerland
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The Netherlands Cancer Institute –
Antoni Van Leeuwenhoekziekenhuis
Erasmus MC - Daniel den Hoed Cancer
Center
Leiden University Medical Centre
University Medical Center Groningen
Centre Hospitalier Universitaire Vaudois
UK
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Christie NHS Foundation Trust
Accrual on 14/03/2012
Accrual graph for step 1
Institution
Number
of
patients
228.Institut Bergonie (FR)
12
234.Centre Oscar Lambret
(FR)
229.Centre G.F.Leclerc (FR)
11
80
8673.Univ Of Iowa Hosp (US)
4
70
259.H.Necker-I.Curie (FR)
3
60
287.C.H.U. De La Timone
(FR)
335.UMCG (NL)
3
235.Centre R.Gauducheau
(FR)
527.Univ. Mannheim (DE)
2
9178.Sarcoma Onco Cter
(US)
9361.Carolinas MC (US)
2
301.N.K.I / A.V.L. A'Dam (NL)
1
3039.Un.C.G.Carus Dresden
(DE)
371.Hosp. Vall D'Hebron
(ES)
906.Med Univ Vienna (AT)
1
Total
53
Accrual of study 62091
120
Theoretical
Study
110
100
Expected today: 71
Observed today: 53
90
50
40
30
20
10
0
28/06/11
27/08/11
26/10/11
25/12/11
Year
23/02/12
23/04/12
22/06/12
5
3
2
2
1
1