Reducing chemotherapy for early-stage breast cancer

Safe De-escalation of Chemotherapy for Stage 1 Breast Cancer

This study is testing if checking blood for tumor DNA can help doctors decide if some early-stage breast cancer patients can safely have less chemotherapy after surgery.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 400 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Royal Marsden NHS Foundation Trust (Academic / other)
• Drugs / interventions: chemotherapy, trastuzumab, pertuzumab, cyclophosphamide
• Locations: 2 sites (London and 1 other locations)
• Trial ID: NCT05058183 on ClinicalTrials.gov

What this trial studies

This study evaluates the presence of circulating tumor DNA (ctDNA) in patients with stage 1 breast cancer who are HER2 positive or triple negative. Blood samples will be collected before and after surgery to analyze ctDNA levels, which can indicate the likelihood of adverse outcomes. The findings aim to help physicians tailor chemotherapy treatments, potentially allowing for reduced chemotherapy intensity while maintaining effective disease management. By identifying patients with residual disease through ctDNA analysis, the study seeks to improve overall disease prognosis.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed stage 1 HER2 positive or triple negative breast cancer.

Not a fit: Patients with stage 1 breast cancer classified as pT1aN0 or those with other breast cancer subtypes may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to less aggressive chemotherapy regimens for patients with early-stage breast cancer, reducing side effects and improving quality of life.

How similar studies have performed: Previous studies have shown promising results in using ctDNA analysis for treatment decisions in various cancers, indicating potential success for this approach in breast cancer.

Eligibility criteria

Inclusion Criteria:

1. Age 18 years or older.
2. Patients with histologically confirmed breast cancer that is either

   A) HER2 positive as defined by 2018 ASCO-CAP guidelines determined by local testing B) Triple negative defined as ER negative (ER staining in \<1% tumour cells or ER Allred score \<3/8) and PR negative (PR staining in \<10% tumour cells or PR Allred score \<6/8) and HER2 negative by 2018 ASCO-CAP guidelines determined by local testing. Patients without PR testing results may enrol on the basis of ER and HER2 results.

   Note that patients negative for ER and PR may enrol whilst awaiting HER2 testing results
3. Stage 1 cancer excluding pT1aN0 cancer, defined as

   A) Patients prior to surgery with primary tumour size on imaging 6-20mm and a normal axilla ultrasound or a biopsy negative axilla

   Patients who enrol prior to surgery will only continue further testing in the trial if their pathological staging fits the after surgery criteria.

   B) Patients after surgery with either
   * Primary tumour size pT1b or pT1c (6-20mm) and pN0 or pN1mi (micrometastasis).
   * Primary tumour size pT1a (1-5mm) and pN1mi

   Note that patients consenting after surgery may not enrol with pT1aN0 stage disease
4. Patients should consent prior to surgery (preferred) or within 2 weeks of surgery. Patients who consent after surgery may extend consent to 4 weeks after surgery, although this will delay the receipt of ctDNA results.
5. Planned and fit enough to receive full standard post-operative chemotherapy, with HER2 targeting as appropriate.
6. Ability to give informed consent and comply with study procedures including blood tests and follow-up for five years.

Exclusion Criteria:

1. Distant metastatic disease.
2. Multifocal invasive cancer
3. Diagnosis of alternative cancer within the last 5 years other than resected non-melanoma skin cancer or cervical intraepithelial neoplasia.
4. Any prior treatment (including neo-adjuvant chemotherapy) for the current breast cancer with the exception of surgical resection for patients enrolling after surgery.
5. Known HIV or hepatitis B or hepatitis C infection.

Where this trial is running

London and 1 other locations

• The Royal Marsden NHS Foundation Trust, Chelsea — London, United Kingdom (Recruiting)
• The Royal Marsden NHS Foundation Trust, Sutton — Sutton, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Nicholas Turner — Royal Marsden NHS Foundation Trust
• Study coordinator: Project Manager

Conditions Breast Cancer