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Not yet recruitingPhase 2

Neu Direction: Testing the Efficacy of Adding HER Inhibition to Standard of Care in Metastatic MLH1-low Endocrine-resistant ER+/HER2- Breast Cancer

Neu Direction: A Single Center Phase II Randomized Clinical Trial to Assess the Efficacy of Adding HER Inhibition to Standard of Care in Patients With Metastatic MLH1-low Endocrine-resistant ER+/HER2- Breast Cancer

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
Female only
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Time periods mentioned: 1 week
  • Procedures mentioned: CT scans, PET scans, Biopsies

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "Patients with endocrine-resistant ER+/HER2- breast cancer who have lesions visible on CT scan will be recruited as they are seen in breast medical oncology and radiation oncology clinics at UC San Diego Health."
  • "Patients will be eligible if they have measurable persistent, recurrent, progressive or metastatic disease on imaging (including FDG PET scan) while on endocrine therapy."
  • "Participants will be stratified by nuclear MLH1 expression on their biopsy tissue using immunohistochemistry."
  • "Neratinib will be administered with a standard ramp up to therapeutic dose to minimize side effects with 120mg daily for 1 week, 160mg daily for 1 week and then 240mg daily thereafter."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests whether adding neratinib, a daily pill, to usual hormone treatment helps control breast cancer that has spread. It is for women whose cancer is ER-positive, HER2-negative, has low MLH1 protein, and has grown despite the first hormone treatment. Researchers will also study side effects.

The goal of this clinical trial is to learn if neratinib, an FDA-approved oral pan-HER2/3/4 inhibitor, improves disease control for participants with metastatic endocrine-resistant ER+/HER2-negative breast cancer. Neratinib is already approved for the treatment of HER2-postive breast cancers. The study will also learn about the safety of adding this drug to standard of care treatments. The main questions it aims to answer are: 1. Does adding neratinib to standard of care systemic therapy improve disease control for patients with metastatic hormone-driven breast cancer that is resistant to endocrine therapy? 2. What side effects do participants have when adding neratinib to standard of care therapy? Researchers will compare standard of care endocrine therapy regimens with and without neratinib to see if neratinib improves control of treatment-resistant metastatic breast cancer that has continued to progress while eon first line endocrine therapy. Participants will: 1. Take standard of care endocrine therapy for metastatic endocrine-resistant breast cancer as determined by their medical oncologist or standard of care therapy with neratinib daily 2. Visit the clinic every 3 months for checkups, tests and imaging studies

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Women older than 18 who are not pregnant, planning pregnancy, or breastfeeding.
  • Breast cancer that has spread and grown during the first treatment, which included hormone treatment. The cancer must be ER-positive (uses estrogen to grow) and HER2-negative (does not have high levels of HER2 protein).
  • At least one cancer spot that has spread must show on a scan. You must be able to have repeat scans.
  • A tissue sample from at least one cancer spot that has spread must confirm ER-positive and HER2-negative cancer within 6 months before screening.
  • The tumor must have low MLH1 protein: fewer than half of its cells test positive for MLH1 in the cell center.
  • The next usual treatment can include any hormone treatment.
  • An ECOG daily activity score above 3, as listed in the study. This scale measures how well you can do daily tasks and care for yourself.
  • Expected to live more than 1 year.

Who can't join

  • A history of using another HER2-targeted treatment at the same time.
  • Currently using another targeted cancer treatment that works throughout the body.
  • A history of another cancer, except non-melanoma skin cancer.
  • Tumor gene testing finds a change that can be treated with a matching targeted drug.
  • No cancer spot visible on a scan that has not already had targeted treatment, such as radiation for symptoms or freezing treatment.
  • A medical reason you cannot take neratinib, including an allergy to it.
  • Severe diarrhea, rated grade 3 or higher, before starting treatment.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Inclusion Criteria: 1. Female over the age of 18 at the time of study enrollment 2. Not pregnant, planning to become pregnant or breast feeding 3. Metastatic ER+/HER2- breast cancer that has progressed on 1st line therapy including endocrine therapy +/- CDK4/6 inhibitors 4. At least one metastatic lesion visible on imaging (including FDG-PET) 5. At least one metastatic lesion must be biopsied and confirmed ER+ and HER2- by immunohistochemistry within 6 months of study screening (HER2 equivocal disease will be confirmed HER2- by FISH) 6. Tumors must be MLH1-low defined by \<50% tumor cells positive for nuclear MLH1 expression on immunohistochemistry 7. Standard of care next line endocrine therapy can include any endocrine therapy 8. Performance status ECOG \> 3 9. Life expectancy \> 1 year 10. Ability to get serial imaging studies Exclusion Criteria: 1. History of concurrent use of other HER2-targeted therapy 2. Concurrent use of other targeted systemic therapy 3. History of other cancers other than non-melanoma skin cancer 4. Actionable mutations on tumor genomic sequencing will be ineligible, and those participants encouraged to proceed with the relevant targeted therapy 5. Participants where there is not at least one imaging apparent lesion that has not been treated with prior targeted therapy (for example palliative radiation or cryoablation) 6. Contraindications to Neratinib use including allergy or hypersensitivity 7. Baseline grade 3+ diarrhea

Study sites (1)

CA