EORTC STBSG

EORTCEGAM, March 2005

EORTC STBSG

Ongoing clinical trials

Venice, November 4th


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 SOCIETYFOR HYPERTHERMIC ONCOLOGY






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)

Registration

6 x VIDE

Randomization

LocalizedGood respSmall tum

VAI vs VAC

LocalizedPoor respLarge tum

VAI vs Bu-mel

Pulm metsPleur mets

VAI + lung RT vs Bu-mel

Stratification:•Age •Local trt of primary

VIDE:•Vincristine•Ifosfamide•Doxorubicin•Etoposide

VAI:•Vincristine•Actinomycin•Ifosfamide

VAC:•Vincristine•Actinomycin D•Cyclophosphamide

Bu-mel:•Busulfan•Melphalan

Study Coordinator: I. Judson, London

Eligibility:•Ewing/PNET•< 50 years•No previous chemo


PROTOCOL 62991-22998: Phase II study of moderate dose radiotherapy for inoperable aggressive fibromatosis

Study coordinator: Ronald KEUS, Arnhem

Radiation dose

# fractions Dose per fraction Fractions per week

56 Gy 28 2 Gy 5 Main endpoint: Absence of local progression 3 years after registration

Eligibility: •Histologically confirmed aggressive fibromatosis•Measurable disease (RECIST)•No current endocrine or chemotherapy, no prior or concurrent limb perf with TNF•>15 years


PROTOCOL 62991-22998: ACCRUAL GRAPH

TheoreticalStudy

Accrual of study 62991

time1/03/061/09/051/03/051/09/041/03/041/09/031/03/031/09/021/03/02

accr

ual

40

35

30

25

20

15

10

5

0

Expected today:40Observed today:29

Expected 1y:10Observed 1y:8Expected 2y:25Observed 2y:14


PROTOCOL 62012: Randomized trial of single agent

doxorubicin versus doxorubicin plus ifosfamide

Randomization

Doxorubicin 75 mg/m² d 1 or As an 72 hour

Contin. i.v. infusion

Doxorubicin25 mg/m² d 1-3

Ifosfamide 2.5 g/m² d 1-4

Neulasta 6mg s.sDay 5

Stratification:•Age (<50 vs ≥50)•PS (0 vs 1)•Liver mets (0 vs +)•Histological grade (2 vs 3)

Study Coordinator: I. Judson, London

Eligibility:•High grade STS (2-3)•Age 16-60•No previous chemo for adv/met dis•WHO PS < 2


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%)


PROTOCOL 62022: Phase II study of Iressa (ZD1839) in locally advanced and/or

metastatic synovial sarcoma

ZD1839 500 mg/day orally once a day for at least 52 weeks

Study Coordinator: J-Y Blay, Lyon

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


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

Randomization

Imatinib mesylate 400 mg/day

during 2 yearsControl Stratification:

•Risk category•Tumour site•Resection level

Study Coordinators: P. CASALI, Milan (ISG) and J-Y BLAY, Lyon (EORTC STBSG)

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

After complete surgery

Main endpoint:•Overall survivalSecondary endpoints:•Relapse-free survival•Relapse-free interval•toxicity

Collaborating Groups: ISG, FSG, EORTC STBSG, GEIS, AGITG


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


PROTOCOL 62024: Stratification factors

Risk category Imatinib

ControlTotal

Intermediate 88 88 176High 120 122 242

Tumour site Imatinib

Control Total

gastric 122 124 246other 86 86 172

Resection level Imatinib

Control Total

R0 185 185 370R1 23 25 48


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).

GLIVEC 400 mg bid for at least 14 weeks

Study Coordinator: A.T. Van Oosterom, Leuven

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


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


Phase II study Phase II study of GW786034 in patients with of GW786034 in patients with

relapsed or refractory relapsed or refractory soft tissue sarcomasoft tissue sarcoma

EORTC study 62043EORTC study 62043


Accrual graph Accrual graph (cut-off 11 Oct ’06)(cut-off 11 Oct ’06)

TheoreticalStudy

Accrual of study 62043

Time (months)1/10/061/08/061/06/061/04/061/02/061/12/05

Num

ber

of p

atie

nts

110

100

90

80

70

60

50

40

30

20

10

0

Expected today:77Observed today:111


Phase II study of E7389 administered as an Phase II study of E7389 administered as an IV infusion day 1 and 8 every 3 weeks in IV infusion day 1 and 8 every 3 weeks in pretreated patients with advanced and/or pretreated patients with advanced and/or

metastatic soft tissue sarcomametastatic soft tissue sarcoma



Trial 62052 Trial 62052

Study Coordinator :Study Coordinator : Dr. Patrick Schoeffski (Leuven, Belgium)

Date of PRC protocol approval:Date of PRC protocol approval: July 17, 2006

Version and date of last amendment: Version and date of last amendment:

first amendment (non-substantial)

protocol version 1.1, August 8, 2006

Treatment scheme :Treatment scheme :

Intravenous bolus of E7389 (1.4 mg/m²) on days 1 and 8 every 21 days


Sample sizeSample 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 stratumSTEP 1: 17 eligible patients per stratum

STEP 2: STEP 2: if > 3 successes in step 1 : continue up to 37 eligible patients if > 3 successes in step 1 : continue up to 37 eligible patients per stratumper stratum


Randomized Phase II study of Randomized Phase II study of brostacillin (PNU-166196A) versus brostacillin (PNU-166196A) versus

doxorubicin as first line doxorubicin as first line chemotherapy in patients with chemotherapy in patients with

advanced or metastatic soft tissue advanced or metastatic soft tissue sarcomasarcoma


Study Coordinator :Study Coordinator : Dr. Hans Gelderblom


Trial 62061 Trial 62061

Date of PRC protocol approval :Date of PRC protocol approval : June 29, 2006

Treatment scheme :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 : Sample Size : 72 (brostacillin) + 36 (doxorubicin)


Main eligibility criteria :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

EligibilityEligibility


End-PointsEnd-Points

Primary: Primary:

6 months progression-free survival

(assessed at 26 weeks)

Secondary:Secondary:

Overall progression-free survival

Overall survival

Objective tumor response (RECIST)

Duration of response


Participating countries

Belgium (3)Belgium (3)

UK (6)UK (6)

France (3)France (3)

The Netherlands (5)The Netherlands (5)

Poland (1)Poland (1)

26 sites in 7 countries

Germany (7)Germany (7)

Slovakia (1)Slovakia (1)

CA & EC approval

CA & EC approval

EC approval

Documents

EORTC STBSG