Summary of Changes
- Change of eligibility criteria to include any patient with newly diagnosed ESFT.
- Addition of analysis of occurrences of ear osteonecrosis to secondary outcome measures.
- Addition of a recommended bone marrow re-assessment for patients with metastatic bone disease, preferably following 2 cycles of VIDE (arm A) or 3 cycles VDC/IE (arm B) induction chemotherapy.
- Addition of a bone marrow sample for biological studies from patients with bone metastatic disease, preferably following 2 cycles of VIDE (if arm A) or 3 cycles of VDC/IE (if arm B) induction chemotherapy.
- Amendment of treatment schedules to allow leeway in timing of chemotherapy and zoledronic acid by +/- 3 days.
- Clarifications to biological studies and inclusion of new analysis that will be performed for research purposes.
- Change of biological studies blood sample timepoint from pre- cycle 3 for all to following cycle 2 and pre-cycle 3 (if arm A) and following cycle 4 and pre-cycle 5 (if arm B) induction chemotherapy.
- Addition of 5ml blood sample at diagnosis for biological studies.
- Addition of two extra blood samples for biological studies - to be taken after completion of zoledronic acid treatment and one year later.
- Clarification that growth parameters will be assessed only for patients entering the second randomisation who are less than 18 years of age.
- Clarification that the first follow-up form is due 18months after randomisation.
- Updated wording in regard to allergic reactions to methylene blue updated.
- Clarification that all SARs should continue to be reported in an expedited manner regardless of how long after IMP administration.
- Removal of Appendix 4 (Declaration of Helsinki) and updated wording regarding ‘Ethical Considerations’.
- Updated personnel contact details and other minor corrections to spelling and wording throughout.
MHRA approval
MHRA cover letter
REC favourable opinion
REC cover letter
Notification of a substantial amendment