Breast cancer Cancer Malignant neoplasm of breast
Conditions
Interventions
Current interventions as of 19/12/2024:
STUDY DESIGN:
The NOSTRA-Feasibility study is a prospective non-randomised, single-arm, multicentre, feasibility study for a proposed future phase III clinica
Sponsors
University of Birmingham
Eligibility
Sex/Gender
Female
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 07/02/2022: 1. Patient with histological diagnosis of operable HER2-positive, ER-negative, early stage invasive breast cancer 2. Tumour size =1cm and visible on US (T1c to T4d) 3. Patient fit and willing to receive a NOSTRA-Feasibility Study approved treatment regimen in the opinion of the responsible clinician. 4. Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1 5. Women of child-bearing potential, prepared to adopt highly effective contraceptive measures if sexually active for at least 6 months after completion of study medication 6. Female, 18 years or older 7. Able to provide written informed consent for the study 8. Availability of embedded paraffin tumour blocks from pre-chemotherapy biopsy 9. The radiology team are able and willing to perform the tumour bed core biopsies Additional Inclusion Criteria for ctDNA Sub-Study 1. Patient has not yet started neoadjuvant treatment. 2. Patient is willing and able to give blood samples as per ctDNA Sub-Study Guidelines _____ Previous inclusion criteria: 1. Patient with histological diagnosis of operable HER2-positive, ER-negative, early stage invasive breast cancer 2. Tumour size = 1cm and visible on US (T1c to T4d) 3. Patient fit and willing to receive one of the three planned NICE approved treatment regimens in the opinion of the responsible clinician 4. Eastern Co-operative Group (ECOG) performance status of 0 or 1 5. Women of childbearing potential, prepared to adopt highly effective contraceptive measures if sexually active for at least 6 months after completion of study medication 6. Female, aged = 18 years 7. Able to provide written informed consent for the study 8. Availability of embedded paraffin tumour blocks from pre-chemotherapy biopsy
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 07/02/2022: 1. Previous ipsilateral invasive breast cancer or Ductal Carcinoma in Situ (DCIS) 2. Unequivocal evidence of distant metastatic disease at registration 3. Multi-focal disease at diagnosis 4. Active malignancy 5. Previous chemotherapy 6. Prior extensive radiotherapy (as judged by the Investigator) to bone marrow 7. Risk factors precluding the safe administration of the intended cytotoxic chemotherapy regimen 8. Patient unsuitable for the planned dual-targeted anti-HER2 treatment in opinion of the Investigator 9. Prior diagnosis of cardiac failure 10. Uncontrolled hypertension, coronary heart disease or other significant cardiac abnormality 11. Bleeding diathesis 12. Any evidence of other disease which in the opinion of the Investigator places the patient at high risk of treatment related complications 13. Pregnant (female patients of child bearing potential must have a urine or blood Human Chorionic Gonadotropin test performed to rule out pregnancy prior to study entry) 14. Patient lactating 15. Patients who have received live vaccine within 4 weeks of the date of study entry 16. Any concomitant medical or psychiatric problems which in the opinion of the Investigator would prevent completion of treatment or follow-up 17. Patient unfit and/or unwilling to undergo surgery 18. Patient unwilling or unable to comply with scheduled visits, treatment plan and study procedures 19. Patient has started protocol non-compliant neoadjuvant chemotherapy 20. Patient has started approved neoadjuvant chemotherapy but insufficient data is available to complete relevant CRFs 21. Patient has already received more than five cycles of approved neoadjuvant chemotherapy _____ Previous exclusion criteria: 1. Previous invasive breast cancer 2. Unequivocal evidence of distant metastatic disease at registration 3. Active malignancy of non-breast origin 4. Previous chemotherapy 5. Prior extensive radiotherapy (as judged by the Investigator) to bone marrow 6. Risk factors precluding the safe administration of the intended cytotoxic chemotherapy regimen 7. Patient unsuitable for the planned dual-targeted anti-HER2 treatment in opinion of the Investigator 8. Prior diagnosis of cardiac failure 9. Uncontrolled hypertension, coronary heart disease or other significant cardiac abnormality 10. Bleeding diathesis 11. Any evidence of other disease which in the opinion of the Investigator places the patient at high risk of treatment related complications 12. Pregnant (female patients of child bearing potential must have a urine or blood Human Chorionic Gonadotropin test performed to rule out pregnancy prior to study entry) 13. Patient lactating 14. Patients who have received live vaccine within 4 weeks of the date of study entry 15. Any concomitant medical or psychiatric problems which in the opinion of the Investigator would prevent completion of treatment or follow-up 16. Patient unfit and/or unwilling to undergo surgery 17. Patient unwilling or unable to comply with scheduled visits, treatment plan and study procedures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. The observed number of patients with false negative biopsies as a proportion of all those assessed will be reported as a proportion of all evaluable patients. 1.1. False negative biopsies are defined as the number of patients in which all core biopsies show no residual tumour but their surgical specimen does contain residual tumour. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Concordance between local and central histopathology reporting of pCR will be defined as the number of patients whose initial local pathological assessment of pCR is confirmed by Central Histopathology Review. 2. Compliance with neoadjuvant and adjuvant treatment; will be assessed by calculating relative dose intensity taking into account of both reductions in dose and delays to treatment. 3. Time to local recurrence; defined as time in whole days from date of registration to local recurrence or death from any cause. Patients who are alive and without local recurrence at the time of analysis will be censored at the date last seen. 4. Time to distant recurrence; defined in whole days from date of registration to distant recurrence or death from any cause. Patients who are alive and without distant recurrence at the time of analysis will be censored at the date last seen. 5. Overall survival; defined in whole days as the date of registration to death from any cause. Patients alive at the time of analysis will be censored at the date last seen. 6. Re-evaluation of the primary outcome using the Central Histopathological Review determination of RCB to define false negative biopsies as RCB-0 or 1 (no tumour or minimal residual disease) in the core biopsies but RCB-2 or 3 in the surgical specimen. This will be reported as a proportion of all recruited patients. 7. Ability of the axillary lymph node assessments post-neoadjuvant chemotherapy to identify definitive axillary lymph node involvement determined by surgery histopathology. Sensitivity, specificity and false negative rates will be reported. | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Outcome results
None listed