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

22. juli 2026 oppdatert av: Asona Juwan Lui, University of California, San Diego

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

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

Studieoversikt

Status

Har ikke rekruttert ennå

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

This is a prospective 2-arm Phase II study testing the efficacy of adding neratinib to standard of care therapy in patients with MLH1-low ER+/HER2- endocrine-resistant breast cancer . 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. At least one lesion must be biopsied and confirmed ER+ by immunohistochemistry and HER2- within 6 months of study screening. Genomic mutation profile will be analyzed along with trial results to identify other potential mutations associated with MLH1 expression and/or neratinib response. Participants will be stratified by nuclear MLH1 expression on their biopsy tissue using immunohistochemistry. MLH1negative (nuclear MLH1 detectable in <5% of tumor cells) and MLH1-low patients (<50% tumor cells positive) hereafter grouped as "MLH1-low" will be randomized to standard of care without (75 participants) or with (75 participants) the addition of neratinib in Arm 1 and Arm 2 respectively . Standard of care therapy can include any endocrine therapy with or without CDK4/6 inhibitors. Prior exposure to CDK4/6 inhibitors is acceptable but not prior HER2-targeted therapy. 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. Treatment response will be monitored via imaging every 3 months while on study and measured using RECIST v. 1.1 criteria and/or mPERCIST criteria as appropriate using FDG-PET. Participants will remain on study until cessation due to side effects or disease progression. Biopsy at disease progression will be encouraged but not required.

Studietype

Intervensjonell

Registrering (Antatt)

150

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studer Kontakt Backup

Studiesteder

  • Forente stater
    • California
      • La Jolla, California, Forente stater, 92037
        • UC San Diego Health Moores Cancer Center
        • Ta kontakt med:
        • Hovedetterforsker:
          • Asona Lui, MD, PhD
        • Underetterforsker:
          • Alyssa Beck, MD
        • Underetterforsker:
          • Svasti Haricharan, PhD

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

  • Voksen
  • Eldre voksen

Tar imot friske frivillige

Nei

Beskrivelse

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

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Enkelt

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Aktiv komparator: Standard of Care
Standard of Care 2nd or 3rd line endocrine therapy with or without CDK4/6 inhibitor
Legemiddel: Endocrine therapy may include one of the following therapies: letrozole, anastrozole, exemestane, tamoxifen or fulvestrant
Endocrine therapy with out without CDK4/6 inhibitor
Legemiddel: CDK4/6 + Endocrine therapy
Endocrine therapy with or without CDK 4/6 inhibitor
Eksperimentell: Stanard of Care + Neratinib
Standard of Care 2nd or 3rd line endocrine therapy with or without CDK4/6 inhibitor + Neratinib
Legemiddel: CDK4/6 + Endocrine therapy
Endocrine therapy with or without CDK 4/6 inhibitor
Legemiddel: Neratinib + endocrine therapy
Neratinib 120mg daily for 1 week, 160mg daily for 1 week and then 240mg daily thereafter
Andre navn:
  • neratinib

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Median Progression-Free Survival
Tidsramme: From enrollment through study completion, an average of 1 year.
From enrollment through study completion, an average of 1 year.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Tidsramme: From enrollment through study completion, an average of 1 year.
Adverse events will be quantified using the CTCAE v4.0 every 3 months
From enrollment through study completion, an average of 1 year.

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

University of California, San Diego

Etterforskere

  • Hovedetterforsker: Asona Lui, MD, PhD, UC San Diego

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Antatt)

1. juli 2027

Primær fullføring (Antatt)

1. mai 2032

Studiet fullført (Antatt)

1. juni 2035

Datoer for studieregistrering

Først innsendt

14. juli 2026

Først innsendt som oppfylte QC-kriteriene

22. juli 2026

Først lagt ut (Faktiske)

27. juli 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

27. juli 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

22. juli 2026

Sist bekreftet

1. juli 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • BC250474 (Annet stipend/finansieringsnummer: Congressionally Designated Medical Research Program (CDMRP), US ARMY MEDICAL RESEARCH ACQUISITION ACTIVITY)
  • 813310 (Annen identifikator: UC San Diego Institutional Review Board (IRB))

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

IPD-planbeskrivelse

Only IPD used in the results publication

IPD-delingstidsramme

Beginning 6 months and ending 3 years after publication of results

Tilgangskriterier for IPD-deling

Proposal that describes planned analyses must be submitted and approved by the Principle Investigator, Asona Lui and data sharing agreement must be signed with the requesters institution. Evidence of IRB approval must be provided by the requestor prior to the sharing of any data.

IPD-deling Støtteinformasjonstype

  • STUDY_PROTOCOL
  • SEVJE
  • ICF

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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