Breast CancerPhase 2NCT04886531
Trial of Pre-operative Neratinib and Endocrine Therapy With Trastuzumab in ER-Positive, HER-2 Positive Breast Cancers
A Phase 2 study testing Neratinib, Letrozole (L) or Anastrozole (A) and Trastuzumab in people with Breast Cancer and HER2-positive Breast Cancer, run by Ruth O'Regan at 4 sites in United States.
Trial summary
Patient will be treated with neratinib, an aromatase inhibitor and trastuzumab for 24 weeks prior to surgery, following an initial 3 weeks of neratinib alone, aromatase inhibitor alone or the combination of neratinib and an aromatase inhibitor. A breast biopsy will be performed prior to Day 1 of week 4 of treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, HER2-positive Breast Cancer, ER Positive Breast Cancer
- What is being tested?
- Neratinib, Letrozole (L) or Anastrozole (A) and Trastuzumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 4 sitesUnited States
- Study dates
- 21 Jul 2022to 21 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must meet all of the following applicable inclusion criteria to participate in this study:
- Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- Age ≥ 18 years at the time of consent.
- Postmenopausal females. NOTE: Postmenopausal status defined as: prior bilateral oophorectomy, Age ≥ 60 years, or Age < 60 years and amenorrhea for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) or an estradiol level in postmenopausal ranges per local reference range.
- ECOG Performance Status of 0-2 within 28 days prior to registration.
- Anatomic, clinical stage I-III, invasive breast cancer, greater than 10mm
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- HER2-positive (by the most recent ASCO-CAP criteria)
- ER positive (≥ 10%). NOTE: There is no requirement for PR status; PR positive or negative allowed.
- Resectable breast cancer in which pre-operative therapy is appropriate (T > 10mm and/or node-positive).
- Archival tissue from the diagnostic pre-treatment biopsy is required. This sample should be identified at screening and shipped by Week 4. If archival tissue is not available, the subject is not eligible for the study.
- Agreeable to repeat breast biopsy at 3 weeks after initiation of treatment.
- Candidate for either letrozole or anastrozole, as determined by the treating physician
- Left ventricular ejection fraction (LVEF) ≥ 50% as assessed by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) documented within 4 weeks prior to the study treatment.
- Demonstrate adequate organ function as defined below; all screening labs to be obtained within 28 days prior to registration.
- Hematological
- Platelet count ≥100,000/uL
- Absolute Neutrophil Count (ANC) ≥1500/uL
- Hemoglobin (Hgb) ≥10 g/dL
- Renal
- ---Calculated creatinine clearance: CrCl ≥30 mL/min using the Cockcroft-Gault formula
- Hepatic
- Bilirubin ≤1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) ≤ 2.5 × ULN
- Alanine aminotransferase (ALT) ≤ 2.5 × ULN
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
- For patients with known serologic evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial.
- Ability of the subject to understand and comply with study procedures for the entire length of the study, as determined by the enrolling physician or protocol designee.
Who cannot join
- Subjects meeting any of the criteria below may not participate in the study:
- Locally advanced or inflammatory breast cancer. NOTE: Locally advanced is defined as Stage IIIC or greater.
- Evidence of metastatic disease. Systemic imaging is not required.
- Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial: exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
- Active infection requiring systemic therapy.
- Requirement for use of a moderate or strong CYP3A4 inhibitor or inducer during the study (see protocol).
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- Treatment with any investigational drug within 14 days prior to registration or within 5 half-lives of the investigational product, whichever is longer.
- Subject has had major surgery within 14 days prior to registration or has not recovered from major side effects of the surgery (tumor biopsy is not considered as major surgery).
- Any impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) or significantly impair the ability to swallow capsules/tablets.
- Known history of myelodysplastic syndrome or acute myeloid leukemia.
- Subjects with any of the following conditions:
- History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 28 days prior to registration.
- Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to registration.
- History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to registration.
- Symptomatic congestive heart failure (New York Heart Association III-IV) or documented current cardiomyopathy with left ventricular ejection fraction (LVEF) <50%.
- Clinically significant cardiac ventricular arrhythmias (e.g. sustained ventricular tachycardia/ventricular fibrillation) or high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block) unless a pacemaker is in place.
- Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome.
- Any concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate subject participation in the clinical study or compromise compliance with the protocol.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 4 recruiting
- Recruiting
University of Illinois Cancer Center
Chicago, Illinois, 60612
Oana Danciu, MD
- Recruiting
Penn State Cancer Institute
Hershey, Pennsylvania, 17033
Cindy Brown, cbrown18@pennstatehealth.psu.edu
Monali Vasekar, MD
- Recruiting
University of Wisconsin
Madison, Wisconsin, 53705
UW Cancer Connect, 800-622-8922
Kari Wisinski, MD
- Recruiting
University of Rochester Medical Center
Rochester, New York, 14642
Lisa Carrozzi, OCN, 585-533-1905, lisa_carrozzi@urmc.rochester.edu
Kathleen Pratt, 585-533-1908, kathleen_pratt@urmc.rochester.edu
About this study
Official title: An Open Label, Phase II Trial of Pre-operative Neratinib and Endocrine Therapy With Trastuzumab in ER-Positive, HER-2 Positive Cancers Hoosier Cancer Research Network BRE17-141
Patient will be treated with neratinib, an aromatase inhibitor and trastuzumab for 24 weeks prior to surgery, following an initial 3 weeks of neratinib alone, aromatase inhibitor alone or the combination of neratinib and an aromatase inhibitor. A breast biopsy will be performed prior to Day 1 of week 4 of treatment. Following surgery, patients will receive standard of care HER2-directed and endocrine therapy at the treating physician's discretion.
- Conditions
- Breast Cancer, HER2-positive Breast Cancer, ER Positive Breast Cancer, PR-Positive Breast Cancer
- Being tested
- Neratinib, Letrozole (L) or Anastrozole (A), Trastuzumab
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeratinibDrug
Also called Nerlynx
120mg for 7 days; 160mg for 7 days ; 240mg for 7 days. 240 mg (up to a maximum of 24 weeks) orally daily*.
Letrozole (L) or Anastrozole (A)Drug
Also called Femara, Arimidex
L: (2.5 mg) OR A: (1 mg) orally daily (up to a maximum of 24 weeks)*
TrastuzumabDrug
Also called Herceptin
All Arms 8mg/kg loading dose followed by 6mg/kg every 3 weeks administered every 3 weeks by IV starting wk 4. Trastuzumab biosimilars may be used per institutional guidelines.
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Weeks 1-3* patients receive either (a) Neratinib, (b) Letrozole or Anastrozole or (c) Neratinib + Letrozole or Anastrozole
Weeks 4-24 patients receive Neratinib + Letrozole or Anastrozole and Trastuzumab
*Starting drug intervention varies for the first 3 weeks depending on arms: a, b, and c by randomization. Receives: Drug: Neratinib; Drug: Letrozole (L) or Anastrozole (A); Drug: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Complete Response (pCR)
pCR is defined as the lack of all signs of invasive cancer in the breast removed during surgery
Measured: 24 weeks
Secondary outcomes (3)
Assess Adverse Events
Assess the adverse events of neratinib in combination with NSAI in subjects
Measured: 24 weeks
Pathological Complete Response (pCR)
Estimate the pCR (ypT0/Tis ypN0) in the breast tissue and lymph nodes
Measured: 24 weeks
Measure Residual Disease
Estimate residual disease in the breast tissue
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2021
- Study start21 Jul 2022
- Primary completion22 Dec 2026 (estimated)
- Study completion21 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ruth O'Regan
- Sponsor type
- University, hospital or other
- Collaborators
- Puma Biotechnology, Inc., University of Rochester
- Responsible party
- Sponsor-investigator, Ruth O'Regan, Hoosier Cancer Research Network
- Investigators
- Ruth O'Regan, MD, Principal investigator, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04886531
- Sponsor's protocol ID
- HCRN BRE17-141
- Status last verified
- Sep 2026
- First submitted
- 10 May 2021
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Phase II Trial of Pre-operative Neratinib and Endocrine Therapy With Trastuzumab in ER-Positive, HER-2 Positive Cancers Hoosier Cancer Research Network BRE17-141
- ClinicalTrials.gov ID
- NCT04886531
- Acronym / sponsor ID
- HCRN BRE17-141
- Conditions
- Breast Cancer, HER2-positive Breast Cancer, ER Positive Breast Cancer, PR-Positive Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Ruth O'ReganUniversity, hospital or other
- Collaborators
- Puma Biotechnology, Inc., University of Rochester
- Study start
- 21 Jul 2022 (actual)
- Primary completion
- 22 Dec 2026 (estimated)
- Study completion
- 21 Dec 2027 (estimated)
- First posted
- 14 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patient will be treated with neratinib, an aromatase inhibitor and trastuzumab for 24 weeks prior to surgery, following an initial 3 weeks of neratinib alone, aromatase inhibitor alone or the combination of neratinib and an aromatase inhibitor. A breast biopsy will be performed prior to Day 1 of week 4 of treatment. Following surgery, patients will receive standard of care HER2-directed and endocrine therapy at the treating physician's discretion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: Neratinib, Drug: Letrozole (L) or Anastrozole (A), Drug: TrastuzumabWeeks 1-3* patients receive either (a) Neratinib, (b) Letrozole or Anastrozole or (c) Neratinib + Letrozole or Anastrozole Weeks 4-24 patients receive Neratinib + Letrozole or Anastrozole and Trastuzumab *Starting drug intervention varies for the first 3 weeks depending on arms: a, b, and c by randomization. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Subject must meet all of the following applicable inclusion criteria to participate in this study:
- Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- Age ≥ 18 years at the time of consent.
- Postmenopausal females. NOTE: Postmenopausal status defined as: prior bilateral oophorectomy, Age ≥ 60 years, or Age < 60 years and amenorrhea for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) or an estradiol level in postmenopausal ranges per local reference range.
- ECOG Performance Status of 0-2 within 28 days prior to registration.
Key exclusion criteria (18 listed)
- Locally advanced or inflammatory breast cancer. NOTE: Locally advanced is defined as Stage IIIC or greater.
- Evidence of metastatic disease. Systemic imaging is not required.
- Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial: exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
- Active infection requiring systemic therapy.
- Requirement for use of a moderate or strong CYP3A4 inhibitor or inducer during the study (see protocol).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NeratinibAlso: Nerlynx120mg for 7 days; 160mg for 7 days ; 240mg for 7 days. 240 mg (up to a maximum of 24 weeks) orally daily*. | Drug | A |
| Letrozole (L) or Anastrozole (A)Also: Femara, ArimidexL: (2.5 mg) OR A: (1 mg) orally daily (up to a maximum of 24 weeks)* | Drug | A |
| TrastuzumabAlso: HerceptinAll Arms 8mg/kg loading dose followed by 6mg/kg every 3 weeks administered every 3 weeks by IV starting wk 4. Trastuzumab biosimilars may be used per institutional guidelines. | Drug | A |
Primary outcome
Pathologic Complete Response (pCR)
Time frame: 24 weeks
pCR is defined as the lack of all signs of invasive cancer in the breast removed during surgery
3 secondary outcomes
Assess Adverse Events
Time frame: 24 weeks
Pathological Complete Response (pCR)
Time frame: 24 weeks
Measure Residual Disease
Time frame: 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ruth O'Regan, MD principal investigator
University of Rochester
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Neratinib, Letrozole (L) or Anastrozole (A) and Trastuzumab in people with Breast Cancer and HER2-positive Breast Cancer, run by Ruth O'Regan at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ruth O'Regan, MD (608-265-9701, ruth_oregan@urmc.rochester.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic Complete Response (pCR) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2026.