Abstract 1526TiP
Background
Older patients with cancer require adequate treatment for which evidence-based data are still scarce. Prolongation of overall survival may not reflect the priority of older metastatic sarcoma patients who, more than younger patients, have a focus on Health-related Quality of life (HRQoL) . Doxorubicin has been the first line treatment for metastatic soft tissue sarcoma (mSTS) based on studies mainly carried out in patients under 65 years. Metronomic chemotherapy, defined as low-dose and frequent administration of cytotoxic drugs, is an alternative that can reduce acute toxicities and prevent tumour regrowth. Therefore, based on the hypothesis that standard doxorubicin-based chemotherapy will result in more toxicities and treatment burden in older mSTS patients, the aim of this study is to demonstrate whether metronomic schedules with cyclophosphamide or doxorubicin achieve better HRQoL outcome.
Trial design
This is a multi-centre, open label, randomized 3-arm phase 3 study in patients with advanced unresectable or metastatic STS, aged ≥ 65 years (patients between 65 and 69 years old are eligible if G8 score ≤ 14). Patients will be randomized to either (1) doxorubicin 60 to 75 mg/m2 every 3 weeks; (2) doxorubicin 12 mg/m2 weekly for a maximum of 450 mg/m2; or (3) cyclophosphamide 100 mg twice daily plus prednis(ol)one 10/20 mg on day 1-7 each 14-day cycle. The primary objective of this study, developed with patient representative contribution, is to assess whether the impact of the disease and its treatment on physical and role functioning can be reduced with metronomic schedules of doxorubicin or cyclophosphamide plus predniso(lo)ne versus the standard doxorubicin treatment. A total of 185 patients are expected to be enrolled in this study, randomized over the three arms in a 1:2:2 ratio so the control arm includes 37 patients and the two experimental arms 74 patients each. The primary endpoint of the study is the difference in physical and role functioning at 12 weeks among the study arms as measured by the QLQ-C30 questionnaire. The first site was activated in April 2022.
Clinical trial identification
EudraCT 2021-000125-27 NCT 04780464.
Editorial acknowledgement
Legal entity responsible for the study
EORTC.
Funding
Rising Tide Foundation, EORTC QLG, FOCA.
Disclosure
W.T.A. van der Graaf: Financial Interests, Institutional, Advisory Board, One advisory board: Bayer; Financial Interests, Institutional, Invited Speaker: Springworks, Ayala; Financial Interests, Institutional, Research Grant, IIS grant: Novartis; Financial Interests, Institutional, Research Grant, IIS: Lilly; Financial Interests, Institutional, Other, consultancy work: Springworks; Non-Financial Interests, , Invited Speaker, President: EORTC; Non-Financial Interests, , Invited Speaker: European Cancer Organisation, Connective Tissue Oncology Society (CTOS); Non-Financial Interests, , Invited Speaker, Chair: Dutch Sarcoma Group, Dutch AYA 'Young and Cancer' Care Network. A. Brunello: Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Other, travel, accomodation: PharmaMar, Takeda, Ipsen. C. Coens: Financial Interests, Institutional, Full or part-time Employment: EORTC HQ. G. Farro: Financial Interests, Institutional, Full or part-time Employment: EORTC HQ. L. Meirsman: Financial Interests, Institutional, Full or part-time Employment: EORTC HQ. All other authors have declared no conflicts of interest.