Summary of protocol changes from protocol v3.0 to 4.0
- Change of chemotherapy backbone: in Europe, the regimen will be selected between FLOT, CapOX por mFOLFOX6; in Asia, cisplatin +capecitabine or 5-FU.
This scientific amendment was necessary after the presentation of the results of the FLOT-4-trial at ASCO 2017, which demonstrated a significantly better progression-free and overall survival for perioperative treatment with FLOT, as compared to ECF. Both, dose modification and supportive care recommendations for treatment with FLOT have been inspired by those used in the FLOT-4 study, which were generously provided by the author. Cisplatin is being kept as an option as it is still standard of care in Korea, and efficacy benefit of other regimen yet have to be demonstrated in these patients (section 4 trial design, page 28; therapeutic drug regimen, section 5; newly added Appendix L).
- A safety run has been introduced in the protocol, given the change of background chemotherapies (section 4.1).
- A definition of ‘high dose corticosteroids’ was inserted (section 3.2).
- Clarification was added, that DPD testing should be done according to local guidelines (section 3.2; section 5.4.5.1.1).
- Dose reduction upon grade 2 or 3 nausea or vomiting has been adapted (appendix L for Cisplatin-treated patients).
- Recommendations regarding the procedures in case of tubular damage and low Mg/Ca were added in Table 9 (Appendix L).
- Measures to be taken after assessment of ototoxicity and sensory neural damage were clarified (Appendix L, section ‘Other precautions’).
Furthermore:
- The numbers of treatment cycles and timelines for follow-up have been clarified and made consistent between the protocol and PISIC.
- For enrolled patients, the side effects and toxicities have been updated in the protocol and PISIC based on the new versions of the IBs of Pertuzumab.
and Trastuzumab.
- A PISIC specific to the new chemotherapy backbone has been created, while the Cisplatin-only PISIC remains valid for Asian patients, as well as already registered patients.
- The RECIST criteria have been added in the protocol.
- Additional clarifications, update of contact information and administrative corrections have been implemented.
Summary of changes from protocol v4.0 to 4.1:
Clarifications included in the protocol about:
- Time Window for tests during the follow up period.
- Treatment administration in case of delay for initiating the adjuvant treatment.