A phase II study of gemcitabine and docetaxel combination in relapsed metastatic or unresectable locally advanced synovial sarcoma.

Synovial sarcoma (SS) is one of the commonest non-rhabdomyosarcoma soft tissue sarcoma with limited treatment options in the relapsed and advanced settings. The combination of gemcitabine and docetaxel has demonstrated its role predominantly in leiomyosarcoma and pleomorphic sarcomas but has not been prospectively studied in SS. This trial assesses the efficacy, tolerability and quality of life (QoL) with this regimen in metastatic/unresectable locally advanced relapsed SS.Patients and methods This was a single-arm, two-stage, phase II, investigator-initiated interventional study among patients with metastatic or unresectable locally advanced SS who had progressed after at least one line of chemotherapy. Gemcitabine 900 mg/m2 on days 1 and 8 and docetaxel 75 mg/m2 on day 8 were administered intravenously every 21 days. The primary endpoint was 3-month progression-free rate (PFR); overall survival (OS), progression-free survival (PFS), overall response rate (ORR), safety and quality of life (QoL) constituted the secondary endpoints.Results Twenty-two patients were enrolled between March 2020 and September 2021 and the study had to be closed early due to slow accrual. The study population comprised of 18 (81.8%) patients with metastatic disease and 4 (18.2%) patients with locally advanced, unresectable disease. The most common primary sites of disease were extremity in 15 (68%) and the median number of lines of prior therapies received was 1 (range 1-4). 3-month PFR was 45.4% (95% CI 24.8-66.1) and ORR was 4.5%. Median progression-free survival (PFS) was 3 months (95% CI 2.3-3.6) and median OS was 14 months (95% CI 8.9-19.0). 7 (31.8%) patients experienced grade 3 or worse toxicities, including anemia (18%), neutropenia (9%) and mucositis (9%). QoL analysis demonstrated significant decline in certain functional and symptom scales, while financial and global health scales remained stable.Conclusion This is the first prospective study on the combination of gemcitabine and docetaxel performed specifically in patients with advanced, relapsed SS. Although the accrual of patients could not be completed as planned, the therapy did produce clinically meaningful outcomes and met its primary endpoint of 3-month PFR. This result, along with the manageable toxicity profile and stable global health status on QoL analysis, should encourage further studies.Trial registration This trial was prospectively registered under the Clinical Trials Registry of India on 26/02/2020 (Registration number: CTRI/2020/02/023612).