NOSTRA-Feasibility Study: A Study Looking at Ultrasound Guided Biopsies for Breast Cancer (NOSTRA)

Can Patients With Residual Cancer After Chemotherapy for Early Breast Cancer be Identified With Multiple Ultrasound-guided Biopsies?

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 (US)-guided tumour bed core biopsies

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Procedure: Tumour bed core biopsy

Detailed Description

The NOSTRA-Feasibility study is designed to 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 trials expert pathologists.

• Study Type: Observational
• Enrollment (Actual): 72

Contacts and Locations

Study Locations

• United Kingdom
  • Belfast, United Kingdom
    • Belfast City Hospital
  • Birmingham, United Kingdom
    • Queen Elizabeth Hospital
  • Birmingham, United Kingdom, B18 7QH
    • City Hospital
  • Blackpool, United Kingdom, FY3 8NR
    • Blackpool Teaching Hospitals NHS Trust
  • Bristol, United Kingdom, BS10 5NB
    • Southmead Hospital
  • Cardiff, United Kingdom, CF64 2XX
    • University Hospital of Llandough
  • Cheltenham, United Kingdom, GL53 7AN
    • Cheltenham General Hospital
  • Dumfries, United Kingdom
    • Dumfries and Galloway Royal Infirmary
  • Edinburgh, United Kingdom
    • Western General
  • Harrow, United Kingdom, HA1 3UJ
    • Northwick Park Hospital
  • Leeds, United Kingdom, LS9 7TF
    • St James's University Hospital
  • Liverpool, United Kingdom, L7 8XP
    • Royal Liverpool Hospital
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital
  • Melrose, United Kingdom, TD6 9BS
    • Borders General Hospital
  • Newcastle Upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital
  • Peterborough, United Kingdom, PE3 9GZ
    • Peterborough City Hospital
  • Poole, United Kingdom, BH15 2JB
    • Poole Hospital
  • Sheffield, United Kingdom, S10 2SJ
    • Weston Park Hospital
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
  • Swansea, United Kingdom
    • Singleton Hospital
  • Upton, United Kingdom, CH49 5PE
    • Arrowe Park Hospital
  • Wigan, United Kingdom, WN1 1RU
    • Thomas Linacre Centre
  • Essex
    • Basildon, Essex, United Kingdom, SS16 5NL
      • Basildon Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

HER-2 positive ER-negative breast cancer patients

Description

Inclusion Criteria:

• 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 fit and willing to receive, or is already receiving and has received no more than five cycles of a NOSTRA-Feasibility Study approved treatment regimen, in the opinion of the responsible clinician
• Eastern Co-operative Group (ECOG) performance status of 0 or 1
• 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, 18 years or older
• Able to provide 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 ipsilateral invasive breast cancer or Ductal Carcinoma in Situ (DCIS)
• Unequivocal evidence of distant metastatic disease at registration
• Multi-focal disease at diagnosis
• Active malignancy
• 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)
• Patient lactating
• 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 protocol non-compliant neo-adjuvant chemotherapy
• Patient has started approved neoadjuvant chemotherapy but insufficient data is available to complete relevant CRFs
• Patient has already received more than five cycles of approved neoadjuvant chemotherapy

Additional Inclusion Criteria for ctDNA Sub-Study

• Patient has not yet started neoadjuvant treatment
• Patient is willing and able to give blood samples as per ctDNA Sub-Study Guidelines

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observed number of patients with false negative biopsies	The observed number of patients with false negative biopsies (i.e. no tumour in the biopsy but tumour in the surgical specimen) as a proportion of all those assessed by Local Histopathology Review.	12 months post last patient recruited

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concordance between Local and Central Histopathology Review of core biopsies	The number of patients whose initial local pathological assessment of pCR is confirmed by Central Histopathology Review.	12 months post last patient recruited
Compliance with treatment	Assessed by calculating relative dose intensity taking into account both reductions in dose and delays to treatment.	12 months post last patient recruited
Time to local recurrence	Defined 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.	Number of days from registration to local recurrence (if within trial duration, approximately 1.5 years)
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 known to be alive.	Number of days from registration to distant recurrence (if within trial duration, approximately 1.5 years)
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.	Whole days from registration to death from any cause (if within trial duration, approximately 1.5 years)
Re-evaluation of the primary outcome using the Central Pathological Review determination of RCB to define false negative biopsies as RCB-0 or 1 (i.e. 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.	Post-last patient last surgery (within approximately 1.5 years of start of trial)
Ability of the axillary lymph node assessments post-neoadjuvant treatment to identify definitive axillary lymph node involvement determined by surgery histopathology	Sensitivity, specificity and false negative rates will be reported.	Post-last patient last surgery (within approximately 1.5 years of start of trial)

Collaborators and Investigators

• Sponsor: University of Birmingham
• Collaborators: Roche Pharma AG; Cancer Research UK
• Investigators: Principal Investigator: Daniel Rea, University of Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2019
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: September 5, 2019
• First Submitted That Met QC Criteria: October 3, 2019
• First Posted (Actual): October 8, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 21, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: breast cancer; HER2 positive; ER negative; Tumour bed core biopsies
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: RG_16-108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No