Transcript PROTOCOL 30012: Randomized phase III Trial Interleukin

EORTC STBSG
Ongoing clinical trials
Venice, November 4th
EGAM, March 2005
EORTC
A RANDOMIZED STUDY COMPARING
NEOADJUVANT CHEMOTHERAPY
ETOPOSIDE + IFOSFAMIDE + ADRIAMYCIN (EIA)
COMBINED WITH REGIONAL HYPERTHERMIA (RHT)
VS.
NEOADJUVANT CHEMOTHERAPY ALONE
IN THE TREATMENT OF HIGH-RISK SOFT TISSUE SARCOMAS IN ADULTS
AN INTERGROUP STUDY WITH THE EUROPEAN SOCIETY
FOR HYPERTHERMIC ONCOLOGY
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EORTC
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EORTC
PROTOCOL 62981: Randomized Phase III study to
evaluate the role of high dose chemotherapy intensification
in the treatment of intermediate prognosis Ewing’s sarcoma
and Primitive Neuroectodermal Tumour (PNET)
Study Coordinator: I. Judson, London
VIDE:
•Vincristine
•Ifosfamide
•Doxorubicin
•Etoposide
Eligibility:
•Ewing/PNET
•< 50 years
•No previous chemo
Registration
6 x VIDE
VAI:
•Vincristine
•Actinomycin
•Ifosfamide
VAC:
•Vincristine
•Actinomycin D
•Cyclophosphamide
Stratification:
•Age
•Local trt of primary
Randomization
Localized
Good resp
Small tum
Localized
Poor resp
Large tum
VAI vs VAC
VAI vs Bu-mel
EGAM, March 2005
Pulm mets
Pleur mets
VAI + lung RT
vs Bu-mel
Bu-mel:
•Busulfan
•Melphalan
EORTC
PROTOCOL 62991-22998: Phase II study of moderate
dose radiotherapy for inoperable aggressive fibromatosis
Study coordinator: Ronald KEUS, Arnhem
Eligibility:
•Histologically confirmed aggressive fibromatosis
•Measurable disease (RECIST)
•No current endocrine or chemotherapy, no prior or concurrent limb perf with TNF
•>15 years
Radiation
dose
56 Gy
# fractions
Dose per fraction
Fractions per week
28
2 Gy
5
Main endpoint:
Absence of local progression 3 years after registration
EGAM, March 2005
EORTC
PROTOCOL 62991-22998: ACCRUAL GRAPH
Accrual of study 62991
40
Theoretical
Study
35
Expected today:40
Observed today:29
30
Expected 1y:10
Observed 1y:8
Expected 2y:25
Observed 2y:14
accrual
25
20
15
10
5
0
1/03/02 1/09/02 1/03/03 1/09/03 1/03/04 1/09/04 1/03/05 1/09/05 1/03/06
time
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EORTC
PROTOCOL 62012: Randomized trial of single agent
doxorubicin versus doxorubicin plus ifosfamide
Study Coordinator: I. Judson, London
Randomization
Doxorubicin
75 mg/m² d 1 or
As an 72 hour
Contin. i.v. infusion
EGAM, March 2005
Doxorubicin
25 mg/m² d 1-3
Ifosfamide
2.5 g/m² d 1-4
Neulasta 6mg s.s
Day 5
Eligibility:
•High grade STS (2-3)
•Age 16-60
•No previous chemo for adv/met dis
•WHO PS < 2
Stratification:
•Age (<50 vs ≥50)
•PS (0 vs 1)
•Liver mets (0 vs +)
•Histological grade (2 vs 3)
EORTC
Study 62012: accrual on 30/10
204 patients
INSTITUTION
Accrual
INSTITUTION
Accrual
E.K.Uni.Tuebingen (DE)
23 (11.3%)
Kl. Grosshadern (DE)
5 (2.5%)
U.Z.Rotterdam (NL)
21 (10.3%)
Umc St Radboud Nijm (NL)
5 (2.5%)
Univ Med Ctr Leiden (NL)
18 (8.8%)
Aarhus Univ.Hosp. (DK)
4 (2.0%)
National Cancer Inst (SK)
15 (7.4%)
H.Univ.Bordet-Erasme (BE)
4 (2.0%)
Royal Marsden Hosp. (GB)
11 (5.4%)
U.Z. Antwerp (BE)
4 (2.0%)
Centre Léon Bérard (FR)
10 (4.9%)
Uni. Koeln (DE)
3 (1.5%)
Kl.Mannheim (DE)
9 (4.4%)
Western inf Glasgow (GB)
3 (1.5%)
U.Z. Leuven (BE)
9 (4.4%)
Hosp Univ San Carlos (ES)
1 (.5%)
Newcastle Gen Hosp. (GB)
8 (3.9%)
Hosp. Vall D’hebron (ES)
1 (.5%)
St James'S Leeds (GB)
8 (3.9%)
Med.Hochsch.Hannover (DE)
1 (.5%)
Az Groningen (NL)
8 (3.9%)
Nottingham Gen/city (GB)
1 (.5%)
Middlesex London (GB)
8 (3.9%)
Queen Elisabeth Birm (GB)
1 (.5%)
Herlev Copenhag. (DK)
7 (3.4%)
Un C.G.Carus Dresden (DE)
1 (.5%)
N.K.I / A.V.L. A'Dam (NL)
7 (3.4%)
Univ. Essen (DE)
1 (.5%)
Weston PK Sheffield (GB)
6 (2.9%)
Western Gen Hospital (GB)
1 (.5%)
EGAM, March 2005
EORTC
PROTOCOL 62022: Phase II study of Iressa
(ZD1839) in locally advanced and/or
metastatic synovial sarcoma
Study Coordinator: J-Y Blay, Lyon
ZD1839 500 mg/day orally once a day for at least 52 weeks
Eligibility:
•Advanced/metastatic synovial sarcoma expressing HER1 Ag (DAKO or another mAb)
•Frozen tissue available for genetic confirmation of the diagnosis and molecular anal.
•One previous line of chemotherapy containing doxorubicin and/or ifosfamide
EGAM, March 2005
EORTC
PROTOCOL 62024: Intermediate and high risk localized, completely
resected, gastrointestinal stromal tumors (GIST) expressing KIT receptor:
a controlled randomized trial on adjuvant Imatinib mesylate (Glivec)
versus no further therapy after complete surgery
Collaborating Groups: ISG, FSG, EORTC STBSG, GEIS, AGITG
Study Coordinators: P. CASALI, Milan (ISG) and J-Y BLAY, Lyon (EORTC STBSG)
After complete surgery
Randomization
Imatinib mesylate
400 mg/day
during 2 years
Control
Eligibility:
•GIST with positive immunostaining for KIT
•Risk of relapse documented on surgical specimen
•No evidence of residual macroscopic disease after surg
•No distant metastases
•WHO PS 0-2, age >17
•No prior radiation therapy /chemotherapy
Stratification:
•Risk category
•Tumour site
•Resection level
Main endpoint:
•Overall survival
Secondary endpoints:
•Relapse-free survival
•Relapse-free interval
•toxicity
EGAM, March 2005
EORTC
PROTOCOL 62024: Accrual by Group
Imatinib
Observation
Total
EORTC STBSG
84
86
170
FSG/FNCLCC
61
67
128
ISG
25
24
49
GEIS
20
21
41
AGITG
18
12
30
Total
208
210
418
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EORTC
PROTOCOL 62024: Stratification factors
Imatinib
Control
Total
Intermediate
88
88
176
High
120
122
242
Imatinib
Control
Total
gastric
122
124
246
other
86
86
172
Imatinib
Control
Total
R0
185
185
370
R1
23
25
48
Risk category
Tumour site
Resection level
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EORTC
PROTOCOL 62027: Phase II study of Glivec (Imatinib) in locally
advanced and/or metastatic soft tissue sarcoma expressing the
t(17;22)(q22;q13) translocation resulting in a COL1A1/PDGF-beta
fusion protein i.e DermatoFibroSarcoma Protuberans (DFSP) and
Giant Cell Fibroblastoma (GCF).
Study Coordinator: A.T. Van Oosterom, Leuven
GLIVEC 400 mg bid for at least 14 weeks
Eligibility:
•Histologically proven locally advanced or metastatic DFSP or GCF
•Progressive disease documented in the last 3 months
•Disease not amenable to surgery, radiation or combined modality treatment
with curative intent
•Frozen tumor or paraffin embedded tissue available for
immunohistochemical, molecular analysis and central path. review
•No prior chemotherapy or no more than 1 line combination chemo with
Ifosfamide and Doxorubicin or 2 lines of single agent therapy or relapsing
within 6 months after end of adjuvant chemo.
•WHO PS 0-2, age 18 years or more
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EORTC
62027 Accrual
Institution
Nb Obs
M.S-K.C.Ctr.Warsaw (PL)
8
Univ Med Ctr Leiden (NL)
3
Christie Manchester (GB)
1
H.Univ.Bordet (BE)
1
Institut Bergonie (FR)
1
U.Z. Leuven (BE)
1
Total
15
EGAM, March 2005
EORTC
Phase II study
of GW786034 in patients with
relapsed or refractory
soft tissue sarcoma
EORTC study 62043
EGAM, March 2005
EORTC
Accrual graph (cut-off 11 Oct ’06)
Accrual of study 62043
110
Theoretical
Study
100
90
Expected today:77
Observed today:111
80
70
60
50
40
30
20
10
0
1/12/05
1/02/06
EGAM, March 2005
1/04/06
1/06/06
Time (months)
1/08/06
1/10/06
EORTC
Phase II study of E7389 administered as an
IV infusion day 1 and 8 every 3 weeks in
pretreated patients with advanced and/or
metastatic soft tissue sarcoma
EORTC study 62052
EGAM, March 2005
EORTC
Trial 62052
Study Coordinator : Dr. Patrick Schoeffski (Leuven, Belgium)
Date of PRC protocol approval: July 17, 2006
Version and date of last amendment:
first amendment (non-substantial)
protocol version 1.1, August 8, 2006
Treatment scheme :
Intravenous bolus of E7389 (1.4 mg/m²) on days 1 and 8
every 21 days
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EORTC
Sample size
The trial will be independently conducted in 4 groups of patients
(strata) :
• Leiomyosarcoma
• Liposarcoma
• Synovial sarcoma
• Other types of eligible STS
STEP 1: 17 eligible patients per stratum
STEP 2:
if > 3 successes in step 1 : continue up to 37 eligible patients
per stratum
EGAM, March 2005
EORTC
Randomized Phase II study of brostacillin
(PNU-166196A) versus doxorubicin as
first line chemotherapy in patients with
advanced or metastatic soft tissue
sarcoma
EORTC study 62061
Study Coordinator : Dr. Hans Gelderblom
EGAM, March 2005
EORTC
Trial 62061
Date of PRC protocol approval : June 29, 2006
Treatment scheme :
max 6 cycles treatment
ARM A : Brostallicin
10 min. IV infusion (10 mg/m²) on day 1 of a q3w
cycle (12.5 mg/m² from second cycle in case of good
tolerance)
ARM B : Doxorubicin
IV bolus (75 mg/m²) on day 1 of a q3w cycle
Sample Size : 72 (brostacillin) + 36 (doxorubicin)
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EORTC
Eligibility
Main eligibility criteria :






Histological or cytological confirmed high or
intermediate grade malignant soft tissue sarcoma
Objective documentation of disease progression
within the last 6 months. Relapsed or refractory
disease incurable by surgery or radiotherapy.
Presence of measurable disease (RECIST).
No prior chemotherapy regimen for advanced or
metastatic disease; (neo)adjuvant therapy is allowed.
At least 60 years of age, or patients at least 18 years
of age non suitable for intensive chemotherapy
combination treatments
WHO performance status 0 or 1
Adequate bone marrow, hepatic and renal function
EGAM, March 2005
EORTC
End-Points
Primary:

6 months progression-free survival
(assessed at 26 weeks)
Secondary:

Overall progression-free survival

Overall survival

Objective tumor response (RECIST)

Duration of response
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EORTC
Participating countries
UK (6)
The Netherlands (5)
CA & EC approval
Belgium (3)
CA & EC approval
Germany (7)
Poland (1)
France (3)
EC approval
26 sites in 7 countries
EGAM, March 2005
Slovakia (1)
EORTC