Multi-Institutional European Phase I/Ii Trial Of Trabectedin Plus Radiotherapy In Metastaticsoft Tissue Sarcoma (Sts) Patients. A Collaborative Spanish (Geis), Italian (Isg) And French (Fsg) Sarcoma Groups Study.

11544 Background: Patients (pts) with advanced STS who require tumor shrinkage beyond first line, have very limited options since the approved drugs exhibit less than 10% of RECIST response. Trabectedin (T) had shown preclinical synergy with radiotherapy (RT). Low-dose RT concurrent with T was conducted in a phase I/II trial as a proof-of-concept of synergy. We present here data from the phase I (pulmonary metastatic cohort) Methods: Pts received T along with RT (30 Gy) in 10 fractions (3Gy/fr). Dose Levels for T were: -1 (1.1 mg/m2), 1 (1.3 mg/m2) and 2 (1.5 mg/m2). Dose level 1 was expanded for a better cardiotoxicity assessment. Dose-limiting toxicity (DLT) were defined as grade ≥3 events excluding G3/4 neutropenia lasting < 5 days, G3 transaminitis if not led to T delay and G3-4 nausea/vomiting due to inadequate prophylaxis. Primary endpoint was response rate according to RECIST Results: From 04/2015 to 06/2017, 18 pts were enrolled. Histologies were: synovial sarcoma in 10 (56%) pts, UPS in 3 (17%), myxoid liposarcoma, dedifferentiated liposarcoma, G3 NOS sarcoma, leiomyosarcoma and MPNST in 1 pts each. Median previous lines 1 (0-3). Twelve pts received T at dose level 1 and 6 pts at level 2. Overall, G 3/4 AEs were: neutropenia (8), ALT elevation (2), GGT elevation (2), anemia (2), febrile neutropenia and pneumonitis (1 each). There were two DLTs: Transient G4 ALT elevation in level 1 and G4 neutropenia ( > 5 days) in level 2. Based on central radiological review and 17 evaluable pts, 2 pts achieved CR (12%), 3 PR (18%), 6 SD (35%), 6 PD (35%). On local review, we found 2 CR (12%), 5 PR (29%), 4 SD (24%), 6 PD (35%). On the irradiated lesions, 4 CR (24%), 8 PR (47%), 4 SD (24%) and 1 PD (5%) were found. With a median FU of 18 m, median PFS was 2.83 (2.3-3.3). Thirteen pts (72%) have died, with a median OS of 8.77 m (3.6-13.9) and 12-month OS rate of 48% Conclusions: T concurrent with RT was feasible in pts with pulmonary metastatic STS regardless of histologic subtype. T at 1.5 mg/m2 is the recommended dose for phase II part. We confirmed the synergy of T+RT, with 71% of the irradiated lesions showing long-lasting dimensional responses. Clinical trial information: NCT02275286.