Objectives To assess the effect of a systematic, fast-track transition from oncological treatment to specialised palliative care at home on symptom burden, to explore intervention mechanisms through patient and intervention provider characteristics and to assess long-term survival and place of death. Measures The effect of a systematic, fast-track transition from oncological treatment to specialised palliative care at home on patient symptom burden was studied in the Domus randomised clinical trial. Participants had incurable cancer and limited treatment options. The intervention was provided by specialised palliative home teams (SPT) based in hospice or hospital and was enriched with a psychological intervention for patient and caregiver dyad. Symptom burden was measured with Edmonton Symptom Assessment System (ESAS-r) at baseline, 8 weeks and 6 months follow-up and analysed with mixed models. Survival and place of death was analysed with Kaplan-Meier and Fisher's exact tests. Results The study included 322 patients. Tiredness was significantly improved for the Domus intervention group at 6 months while the other nine symptom outcomes were not significantly different from the control group. Exploring the efficacy of intervention provider demonstrated significant differences in favour of the hospice SPT on four symptoms and total symptom score. Patients with children responded more favourably to the intervention. The long-term follow-up demonstrated no differences between the intervention and the control groups regarding survival or home deaths. Conclusions The Domus intervention may reduce tiredness. Moreover, the intervention provider and having children might play a role concerning intervention efficacy. The intervention did not affect survival or home deaths. Trial registration number NCT01885637