Neo-RT: A Study Investigating Whether Changing the Sequence of Treatments (Starting Radiotherapy Followed by Hormone Therapy Before Surgery) is Feasible (Neo-RT)

Neo-RT: Pre-operative Breast Intensity Modulated Radiotherapy in Patients Receiving Neo-adjuvant Hormonal Treatment for Breast Cancer - a Feasibility Study.

Four in 10 women diagnosed with breast cancer undergo mastectomy with or without breast reconstruction and less than half are satisfied with how they look unclothed. Breast conservation (removing the area with the lump only) can offer less extensive surgery and improved breast appearance, which can therefore increase well-being.

Intensity-modulated radiotherapy (IMRT) closely shapes the radiation beam to the cancer and is currently given after breast surgery. A new combination of IMRT followed by hormone treatment given before surgery, may increase the possibility of breast conservation.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Intensity modulated radiotherapy (IMRT); Drug: Endocrine therapy; Procedure: Breast conserving surgery

• Study Type: Observational
• Enrollment (Anticipated): 43

Contacts and Locations

• Study Contact: Name: Victoria Ingleson, BSc; Phone Number: 01223 349702; Email: victoria.ingleson@addenbrookes.nhs.uk
• Study Contact Backup: Name: Anne-Laure Vallier; Phone Number: 01223 348086; Email: anne-laure.vallier@addenbrookes.nhs.uk

Study Locations

• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Recruiting
      • Cambridge University Hospitals NHS Foundation Trust
      • Contact: Anne-Laure Vallier; Phone Number: 01223 348086; Email: anne-laure.vallier@addenbrookes.nhs.uk
      • Contact: Meena Murthy, BSc; Phone Number: 01223 349702; Email: meena.murthy@addenbrookes.nhs.uk
      • Principal Investigator: Charlotte Coles

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Women with invasive breast cancer for planned treatment with neo-adjuvant endocrine therapy, where radiotherapy may make breast conserving surgery easier.

Description

Inclusion Criteria:

• Written informed consent to participate
• Female
• Aged 18 years and older
• ECOG performance status 0-2
• Histology confirmed invasive breast cancer
• ER positive (Allred score 6-8)
• HER2 negative
• Palpable size ≥20mm
• Grade I-II (or grade III if considered not suitable for neo-adjuvant chemotherapy)
• Considered that radiotherapy will make breast conserving surgery easier
• No evidence of non-breast malignancy if treated with curative intent unless the patient has been disease free ≥5 years
• Unifocal or multifocal disease, i.e. tumour in the same quadrant and breast conserving surgery still feasible

Exclusion Criteria:

• Contraindications to breast radiotherapy or neo-adjuvant endocrine therapy
• Bilateral breast cancer
• Metastatic cancer
• Multicentric disease
• Concomitant medical/psychiatric problems preventing completion of study treatment or follow-up
• Pregnancy
• Breast feeding

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients successfully completing neo-adjuvant IMRT and endocrine treatment followed by beast surgery, as per study protocol.	Successful completion of IMRT is defined as: Treatment received was either 48 Gy/15# or 40 Gy/15# with sequential boost; Treatment received was 'other', but the reason for different schedule was not due to toxicity related from the radiotherapy; Radiotherapy treatment was not delayed by 5 days or more; Radiotherapy treatment was delayed by 5 days or more, but the reason was not due to toxicity related from the radiotherapy Successful completion of endocrine treatment is defined as: Patient received at least 80% of endocrine treatment received; Patient did not receive 80% of endocrine treatment, but the reason was not due to toxicity or toxicity related from radiotherapy or endocrine Successful surgery is defined as: Planned date of surgery is not delayed; Planned date of surgery is delayed, but the reason was not due to toxicity or toxicity related to radiotherapy or endocrine treatment.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute radiotherapy toxicity following IMRT, assessed by CTCAE v4.03	Acute radiotherapy toxicity following IMRT, assessed by CTCAE v4.03	3 weeks
Mastectomy rate	Analysis will be descriptive, and in accordance to the statistical analysis plan.	6 months
Peri/post operative complications	Including: Length of stay; Unplanned return to theatre (and reason); Use of antibiotics for wound related issues; Number of clinic attendances for wound related problems	9 months
Volume of residual tumour and response to treatment	There will be a central review (2 readers) of all primary surgery histopathology reports for the secondary endpoint of pathological complete response (pCR). The histopathology slides from the surgical resection will be requested for central assessment of residual disease for all cases where there has not been a pCR. The variables that will be recorded include residual invasive tumour size in two dimensions, residual invasive tumour cellularity, number of lymph node metastases and size of the largest metastasis. A representative tumour tissue block will be selected and requested from the laboratory. Sections from the block will be taken for staining with ER and Ki67 to allow calculation of the histological assessment of residual tumour burden, and cores taken as per the protocol.	6 months
Late normal tissue toxicity, as assessed by: 1) clinicians	Clinician - post-radiotherapy questionnaire (with permission from IMPORT Trial Management Group and Dr Penny Hopwood)	Annually for 5 years
Late normal tissue toxicity, as assessed by: 2) Patient Reported Outcome Measurements (PROMs)	Patient Reported Outcome Measure - Validated Breast-Q questionnaire	Annually for 5 years
Late normal tissue toxicity, as assessed by: 2) Patient Reported Outcome Measurements (PROMs)	Patient Reported Outcome Measure - EORTC IL1 Modified BRECON23 PROM questionnaire.	Annually for 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory research will be carried out to identify possible molecular and radiological biomarkers of response	Exploratory investigation of potential biomarkers include: ctDNA,; PBMCs,; Tumour molecular profiles,; Immunohistochemical/immunofluorescence markers of: Immune response (TILs) Tumour proliferation (Ki67, Geminin) DNA damage response and cell cycle checkpoint activation (including 53BP1, RAD51, ATM1, BRCA1, p53, p21 and p-chk-1) Tumour microenvironment (hypoxia) - Multiplexed single cell proteomics of both cellular suspensions (including whole blood) and intact tissues, to investigate the immune response and other novel markers Since the identification of new biomarkers correlating with disease activity and the efficacy or safety of treatment is rapidly evolving, the definitive list of biomarkers remains to be determined. However they will be detailed in an appropriate analysis plan prior to undertaking any sample analysis.	6 months post last patient recruited

Collaborators and Investigators

• Sponsor: CCTU- Cancer Theme
• Collaborators: Breast Cancer Now; CRUK Cambridge Institute
• Investigators: Principal Investigator: Charlotte E Coles, MB ChB, MRCP, FRCR, PhD, University of Cambridge

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2018
• Primary Completion (Anticipated): April 30, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: July 24, 2018
• First Submitted That Met QC Criteria: January 25, 2019
• First Posted (Actual): January 28, 2019

Study Record Updates

• Last Update Posted (Actual): July 27, 2021
• Last Update Submitted That Met QC Criteria: July 26, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: Neo-RT

Drug and device information, study documents

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