1517TiP - Randomized, Open, Prospective, Phase II Clinical Trial of Doxorubicin (DOXO) vs. Trabectedin Plus Doxo in the First-Line Treatment of Patients (PTS) with Advanced Non-Operable and/or Metastatic Soft Tissue Sarcomas (STS): Geis-20 Study

Abstract

ABSTRACT Background Advanced STS are rare diseases that need development of efficacious new treatments, as exemplified by doxorubicin still being the reference standard after 30 years of existence. Trabectedin is a new antineoplastic with a novel mechanism of action that obtained in 2007 the Marketing Authorization in Europe for the treatment of STS after anthracycline and ifosfamide failure, or in pts unsuited to receive these drugs. The academic GEIS-20 study arises from the need to bring to the first-line of treatment of advanced STS agents that have shown activity in second-line. The combination Doxo and trabectedin, drugs with different mechanisms of action and potential synergy, may be a clear advantage to obtain better results. The toxicity profiles of both study drugs are different; worsening or cumulative adverse effects are not expected. Methods The GEIS-20 is an ongoing phase II, randomized, open label and multicentre (27 centres) study in the first-line setting conducted in Spain and Portugal. This trial, lead by the Spanish Sarcoma Group, has started pts enrolment in Arm A (control): Doxo 75 mg/m2 20 min i.v. infusion; and Arm B (experimental): Trabectedin 1.1 mg/m2 3-h i.v. infusion + Doxo 60 mg/m2 20 min i.v. infusion + i.v. dexamethasone pre-treatment. Both treatments are given every 3 weeks for a maximum of 6 cycles. Sample size: 182 pts. The primary endpoint is to compare the radiological progression-free survival between arms. Secondary endpoints include the evaluation of response (RECIST v.1.1), tumor control rate, overall survival, activity per Choi criteria, toxicity and pharmacogenomics. Key eligibility criteria: Chemo-naive pts with advanced, non operable and/or metastatic STS, aged 18-70 years, with performance status ≤1, normal cardiac, renal, haematological functions and liver function tests. Pts are stratified by metastatic disease free interval ≤12 months vs. >12 months. A central pathology and radiology review will be performed. Disclosure A.M. Poveda: I was compensated as consultant from PharmaMar. All other authors have declared no conflicts of interest.