NOSTRA

Overview

A prospective multi-centre, non-randomised, single-arm feasibility study to inform a future phase III randomised trial.

Overview

To determine whether patients with residual cancer can be identified by histological examination of multiple ultra sound-guided tumour bed core biopsies following dual-targeted neoadjuvant treatment for HER2-positive, ER-negative early primary breast cancer.

Inclusion Criteria

• Adult females with HER2 +ve, ER-ve, tumour size >1cm early breast cancer visible on ultrasound. Fit for chemotherapy, dual targeted anti HER2 therapy and surgery.
• Patient with histological diagnosis of operable HER2-positive, ER-negative, early stage invasive breast cancer
• Tumour size ≥ 1cm and visible on US (T1c to T4d)
• Patient already started approved chemotherapy, has received five or fewer cycles, has had baseline investigations and this data can be collected retrospectively.
• Patient fit and willing to receive one of the approved treatment regimens in the opinion of the responsible clinician/OR patient already started approved chemotherapy, has received five or fewer cycles, has had baseline investigations
• 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
• Female, aged ≥ 18 years
• Able to provide written informed consent for the study
• Availability of embedded paraffin tumour blocks from pre-chemotherapy biopsy
• The radiology team are able and willing to perform the tumour bed core biopsies

Exclusion criteria

• Previous invasive breast cancer
• Unequivocal evidence of distant metastatic disease at registration
• Active malignancy of non-breast origin
• Previous chemotherapy
• Prior extensive radiotherapy (as judged by the Investigator) to bone marrow
• Risk factors precluding the safe administration of the intended cytotoxic chemotherapy regimen
• Patient unsuitable for the planned dual-targeted anti-HER2 treatment in opinion of the Investigator
• Prior diagnosis of cardiac failure
  Uncontrolled hypertension, coronary heart disease or other significant cardiac abnormality
• Bleeding diathesis
• Any evidence of other disease which in the opinion of the Investigator places the patient at high risk of treatment related complications
• 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)
• Lactating patients
• Patients who have received live vaccine within 4 weeks of the date of study entry
• Any concomitant medical or psychiatric problems which in the opinion of the investigator would prevent completion of treatment or follow-up
• Patient unfit and/or unwilling to undergo surgery
• Patient unwilling or unable to comply with scheduled visits, treatment plan and study procedures
• Patient has started non-protocol compliant neo-adjuvant chemotherapy
• Patient has started approved neo-adjuvant chemotherapy but retrospective data is not available
• Patient has received more than five cycles of approved neo-adjuvant chemotherapy

Planned sample size

150 Patients will be recruited over 18 months with a 12 month treatment period

Total number of sites planned

30 sites

Timeline

NOSTRA end of recruitment date has now been extended till the end of December 2023. 

Patients will followed-up at 12 months and at 5 years.