NOSTRA

Trial Info

Status: Open

Specialty: Breast

Date Opened: 24/03/2021

Planned Close Date: 14/05/2025

Sponsor: University of Birmingham

Principal Investigator: Dr Bezecny

Trial Description

Approximately 15% of early breast cancer patients in the UK have HER2-positive tumours. Within the neoadjuvant population HER2-positive cases split roughly 50:50 between ER-positive and ER-negative disease; thus an estimated 6-7.5% of all operable breast cancer patients have tumours with the HER2-positive, ER-negative phenotype. In the UK, this is approximately 3500 patients per year. At least half of these patients would be candidates for a dual-targeted therapy (a combination of neoadjuvant chemotherapy plus two anti-HER2 therapies), which results in consistently high pathalogical Complete Response (pCR) rates in the region of 70-80%, which are linked to good outcome. Patients with operable early stage breast cancer treated with neoadjuvant treatment always undergo surgery, regardless of their response to treatment. These patients are thus an appropriate group in which to initially explore omitting surgery.

The NOSTRA-Feasibility study is designed as a prerequisite to the conduct of a randomised phase III study which will determine if it is safe to omit surgery after the planned neoadjuvant chemotherapy plus dual-targeted anti-HER2 treatment. The study is needed to determine whether patients with residual cancer can be identified by histological examination of multiple ultrasound-guided tumour bed core biopsies following dual-targeted neoadjuvant treatment for HER2-positive, ER-negative early primary breast cancer and whether there is concordance between local pathology reporting and central pathology reporting by the trial’s expert pathologists. 150 patients with early breast cancer will enter the study from hospitals around the UK to one of the three National Institute of Clinical Excellence (NICE) approved treatment regimens involving neoadjuvant chemotherapy plus dual-targeted anti-HER2 treatment.

The study encompasses an important translational research component, which involves the collection of diagnostic biopsies, tumour bed core biopsies and surgical excision specimens (including axilla biopsy specimen and SLNB specimen). Also incorporated into the study is collection of blood samples for the optional ctDNA substudy.

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 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, 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

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

Contacts

Research Nurse: Emma Davies (Ext No. 55649) Emma.Davies16@nhs.net

Administrator: Arun Prakash

Link to EDGE

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