Lines of Research: 1. High-dose Ifosfamide

Spanish Group for Research on Sarcoma (GEIS)

Grupo Español de Investigación en Sarcomas Grupo Español de Investigación en Sarcomas

Current Lines of Research

Clinical and Translational Studies

Lines of Research: 1. High-dose Ifosfamide

Clinical Studies Performed

- Phase II of HD Ifosfamide in first-line treatment 45 pts RR 38% (JM Buesa. Ann Oncol 1998) - Phase II of the combination of HD Ifosfamide and Doxorubicin

65 pts RR 40% (A López Pousa. Sarcoma 2006) - Phase II of sequential dose-dense Doxorubicin and Ifosfamide

60 pts RR 38% (J Maurel. Cancer 2004)

- Study of Prognostic Factors in pts treated with HD Ifosfamide (J Maurel. J Surg Oncol 2004) Ongoing Study

- Phase II study of neoadjuvant high-dose ifosfamide and radiotherapy in high-risk localized STS

Spanish Group for Research on Sarcoma (GEIS)

Lines of Research: 1. High-dose Ifosfamide

Lines of Research: 2. Studies on new drugs in STS

Clinical Studies Performed

- TEMOZOLOMIDE: Phase II in a 6 week extended schedule in 2nd- line STS (X Garcia del Muro, Cancer 2005) - TEMOZOLOMIDE: Phase II in first-line gynecological sarcoma

(X Garcia del Muro, ASCO 2006)

- GEMCITABINE: Phase I-II of the combination of Doxorubicin and Gemcitabine in first-line ST (A López Pousa. Br J Cancer 2006)

- GEMCITABINE: Phase I of the combination of Gemcitabine and DTIC in STS (JM Buesa. Cancer 2004) - CAELYX: Phase II study in second-line STS

27 pts RR 2 EE 12 (A Poveda. Sarcoma, 2007) Ongoing Studies

- LIPOSOMAL DOXORUBICIN in pts older than 65 y. (first-line)

- SORAFENIB: Phase I/II in combination with Ifosfamide in STS

Lines of Research: 2. Studies on new drugs in STS

113 pts from 18 centers

Study Design: Randomized phase II. Endpoint: PFR at 3 months ARM A: DTIC 1200 mg/m² q 21 days

ARM B: Gemcitabine 1800 mg/m² + DTIC 500 mg/m² q 14 day

Randomized phase II study of DTIC plus Gemcitabine versus DTIC Randomized phase II study of DTIC plus Gemcitabine versus DTIC

alone in patients with pretreated Soft Tissue Sarcoma alone in patients with pretreated Soft Tissue Sarcoma

PROGRESSION FREE SURVIVAL

Probability of Progression Free Survival

Months

p = 0.005

Arm A: DTIC

Arm B: Gemcitabine + DTIC

[0.39 - 0.856]

0.579 [2.47 - 5.9]

4.2 m.

Arm B

0.005 1 [1.25 - 2.75]

2 m.

Arm A

CI 95%

HR p value CI 95%

PFS median

OVERALL SURVIVAL

Probability of Overall Survival

Months Arm A: DTIC

Arm B: Gemcitabine + DTIC

p = 0.014

[0.35 - 0.897]

0.563 [8.78 – 24.88]

16.8 m.

Arm B

0.014 1 [6 – 10.4]

8.2 m.

Arm A

CI 95%

HR p value CI 95%

OS median

(X Garcia del Muro.ASCO 2009)

Lines of Research: 3. Studies in GIST

GIST: CLINICAL AND TRANSLATIONAL STUDIES Recently Closed Clinical Trial

- Phase I/II Clinical trial of Imatinib and low-dose

Doxorubicin in refractory GIST (A Poveda. ASCO 2008)

Intergroup Collaboration

- Phase III study of adjuvant Imatinib versus observation in resected localized GIST of high-risk

Translational Study

- Deletions affecting codons 557-558 of the c-KIT gene

indicate a poor prognosis in patients with resected GIST

(J Martín. J Clin Oncol 2005 /

ASCO 2008)

GEIS Future Projects and Educational Tasks

• CLINICAL TRIALS OF NEW DRUGS:

• Phase II randomized trial of Trabectedin and Doxorubicin versus Doxorubicin alone in first-line STS

• Phase II randomized trial of Gemcitabine and Rapamycin versus Gemcitabine alone in pretreated STS

• TRANSLATIONAL TRIALS IN STS AND GIST

• STUDIES IN BONE SARCOMAS

• EDUCATIONAL TASKS:

• Annual GEIS Simposium

• Advanced Course in Sarcomas for fellows and young oncologists

• Guidelines in GIST and STS

Spanish Group for Research on Sarcoma (GEIS)