Clinical trial NCT04118192: NOSTRA-Feasibility Study: A Study Looking at Ultrasound Guided Biopsies for Breast Cancer
Official title: Can Patients With Residual Cancer After Chemotherapy for Early Breast Cancer be Identified With Multiple Ultrasound-guided Biopsies?
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Breast Cancer
Keywords: breast cancer
HER2 positive
ER negative
Tumour bed core biopsies
Lead sponsor: University of Birmingham
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
name: Cancer Research UK
First posted: 2019-10-08
Enrollment: 72
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: HER-2 positive ER-negative breast cancer patients

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Observed number of patients with false negative biopsies
timeFrame: 12 months post last patient recruited
Secondary outcomes:
measure: Concordance between Local and Central Histopathology Review of core biopsies
timeFrame: 12 months post last patient recruited
measure: Compliance with treatment
timeFrame: 12 months post last patient recruited
measure: Time to local recurrence
timeFrame: Number of days from registration to local recurrence (if within trial duration, approximately 1.5 years)
measure: Time to distant recurrence
timeFrame: Number of days from registration to distant recurrence (if within trial duration, approximately 1.5 years)
measure: Overall survival
timeFrame: Whole days from registration to death from any cause (if within trial duration, approximately 1.5 years)
measure: 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
timeFrame: Post-last patient last surgery (within approximately 1.5 years of start of trial)
measure: Ability of the axillary lymph node assessments post-neoadjuvant treatment to identify definitive axillary lymph node involvement determined by surgery histopathology
timeFrame: Post-last patient last surgery (within approximately 1.5 years of start of trial)
Other outcomes:
Locations:
city: Basildon
country: United Kingdom
facility: Basildon Hospital
state: Essex
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Birmingham
country: United Kingdom
facility: City Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Blackpool
country: United Kingdom
facility: Blackpool Teaching Hospitals NHS Trust
city: Bristol
country: United Kingdom
facility: Southmead Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital of Llandough
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
city: Dumfries
country: United Kingdom
facility: Dumfries and Galloway Royal Infirmary
city: Edinburgh
country: United Kingdom
facility: Western General
city: Harrow
country: United Kingdom
facility: Northwick Park Hospital
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Melrose
country: United Kingdom
facility: Borders General Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Peterborough
country: United Kingdom
facility: Peterborough City Hospital
city: Poole
country: United Kingdom
facility: Poole Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Swansea
country: United Kingdom
facility: Singleton Hospital
city: Upton
country: United Kingdom
facility: Arrowe Park Hospital
city: Wigan
country: United Kingdom
facility: Thomas Linacre Centre
Study officials:
affiliation: University of Birmingham
name: Daniel Rea
role: PRINCIPAL_INVESTIGATOR
References: