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

Recruitment end date May 2021.

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