HER2-RADiCAL

Overview

HER2-RADiCAL is a response-directed interventional cohort (single group) study. It uses treatment response (pCR) following neoSACT as a marker for selective therapy reduction.

Patients with HER2-postive (HER2+) early breast cancer who have recently completed neoSACT with chemotherapy plus trastuzumab and pertuzumab and where no evidence of residual invasive cancer has been found at surgery either in the breast or sampled regional nodes (pCR; ypT0/Tis ypN0 M0) will be invited to participate.

All patients registered into the study will continue trastuzumab to complete a total of 9 cycles (approximately 6 months treatment) inclusive of those cycles administered in the (neo-) adjuvant setting prior to study entry. No further pertuzumab will be administered and no adjuvant chemotherapy is permitted. All patients will receive adjuvant radiotherapy, bisphosphonates and endocrine therapy as per local practice.

Objectives

Primary Objective

• To determine the efficacy of response-adapted (reduced) therapy in patients who at presentation have HER2+ early breast cancer with intermediate risk of recurrence, and by virtue of achieving pCR (ypT0/is ypN0) following neo-adjuvant systemic chemotherapy and dual antibody therapy (trastuzumab and pertuzumab) are reclassified as being at low risk of recurrence.

Secondary Objectives

• To determine adherence/acceptability to/of the response-adapted treatment pathway.
• To describe the observed current standard of care treatment pathway using UK population level routine NHS data.
• To estimate the cost-effectiveness of response adapted therapy in comparison to both hypothetical maximal therapy and to observed standard therapy within the UK NHS.

Exploratory Objective

• Explore potential tumour biomarkers associated with recurrence. 

Inclusion/ exclusion criteria

Key Inclusion Criteria

• HER2+ early breast cancer
• Initial diagnostic stage T1N1 or T2N0-1
• Locally-determined pCR (ypT0/Tis ypN0)
• Multifocal and/or bilateral cancers are permitted provided at least one meets inclusions and none meet any inclusions

Key Exclusion Criteria

• Evidence of metastatic disease at any time since diagnosis
• Any residual invasive disease following neoSACT
• Evidence of scarring (or other pathological features consistent with previous malignant involvement) in ≥4 axillary nodes or clinical nodal stage N≥2 at any time
• Positive SLNB pre-neoSACt
• Previous breast carcinoma diagnosis 

Planned sample size

The aim is to recruit 720 participants from 40 sites nationally over three and a half years. The predicted end date for all study activities is 28/02/2030.

Contact information

ICR-CTSU HER2-RADiCAL Trial Manger

Email: her2radical-icrctsu@icr.ac.uk

Telephone: 020 8722 4185