NOSTRA

A prospective non-randomised, multi-centre feasibility study to assess if patients with residual cancer following dual-targeted neoadjuvant chemotherapy treatment for HER2-positive, ER-negative early breast cancer can be identified by multiple ultrasound-guided tumour bed core biopsies

Overview

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

Objectives

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

Key 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 2022. 

Follow up

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


Contact information and website

NOSTRA website

CRUK website

Email: NOSTRA@trials.bham.ac.uk

Trial flyer