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Anatomic Stage I Breast CancerPhase 2NCT05919108

Neoadjuvant Neratinib in Stage I-III HER2-Mutated Lobular Breast Cancers

A Phase 2 study testing Endocrine Therapy, Biopsy of breast and Neratinib in people with Anatomic Stage I Breast Cancer and Anatomic Stage II Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 5 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This phase II trial tests how well neratinib prior to the primary treatment (neoadjuvant) works in treating patients with stage I-III HER2 mutated lobular breast cancers. Neratinib is in a class of medications called kinase inhibitors. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Endocrine Therapy, Biopsy of breast and Neratinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
5 sitesUnited States
Study dates
11 Jun 2024to 30 Apr 2031
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

  • Each patient will be entered into this study only if all of these criteria are met:
  • Subjects aged 18 years or older at signing of informed consent.
  • New diagnosis of clinical stage I-III HR+ histologically-proven (i.e. absent or decreased e-cadherin expression) invasive lobular carcinoma
  • Synchronous breast tumors are permitted as long as the synchronous tumor is ER+ and HER2-negative.
  • ER+ disease defined as ≥1% estrogen receptor (ER) positive consistent with current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) or European Society of Medical Oncology (ESMO) guidelines)
  • At the time of screening, histologically confirmed cancers in patients with previously documented activating HER2 mutation (see Appendix A) confirmed by a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalent laboratory.
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  • Archival tissue availability (if not available a fresh tumor biopsy will be required) and subject must agree to submission of sample for central testing
  • Minimum tumor size of ≥1.5 cm by US, mammogram, MRI imaging, or clinical breast exam
  • ECOG performance status 0 or 1
  • Patients must have adequate hematologic, hepatic, and renal function. All laboratory tests must be obtained within 1 month of study entry. This includes:
  • Estimated glomerular filtration rate of ≥50 mL/min
  • Albumin ≥ 2.5 g/dL
  • ANC ≥1500/mm^3
  • Platelet count ≥100,000/mm^3
  • HgB ≥ 9 g/dL
  • Total serum bilirubin ≤ 1.5 x ULN (in patients with known Gilbert Syndrome, a total bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN)
  • AST and ALT ≤ 3 x ULN
  • Pre-, peri-, or post-menopausal, confirmed by history or laboratory testing as needed
  • Diagnostic biopsy tissue availability with sufficient tumor to permit NGS (if not available, a fresh biopsy will be required)
  • No prior treatment for current diagnosis of breast cancer
  • For patients who are not postmenopausal (women) or surgically sterile (absence of ovaries and/or uterus or vasectomy), agreement to remain abstinent or to use two adequate methods of contraception (e.g., condoms, diaphragm, vasectomy/vasectomized partner, tubal ligation), during the treatment period and for at least 30 days after the last dose of study treatment. Hormone based oral contraceptives are not allowed on study. Postmenopausal is defined as:
  • Age ≥ 55 years
  • Age ≤ 55 years and amenorrheic for 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression; or follicle stimulating hormone and estradiol in the postmenopausal range. Female participants of childbearing potential are eligible to participate if they agree to use a highly effective method of contraception that has a low user dependency consistently and correctly.
  • Note: The effects of neratinib on the developing fetus are unknown and endocrine therapy is contraindicated in pregnancy. For this reason and because teratogenic effects have been observed in nonclinical studies and neratinib, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of the study participation, and for 1 month after the last dose of study medication. Should a woman become pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation and 3.5 months after completion of study treatment.

Who cannot join

  • Evidence of distant metastatic disease
  • Synchronous breast cancer that is estrogen receptor negative OR HER2-amplified OR requires treatment with neoadjuvant chemotherapy per the judgement of the treating physician
  • Patients harboring ineligible somatic HER2 mutations, such as those that are subclonal in nature or those resulting in the expression of truncated proteins including alterations that result in premature stop codon or a change in reading frame (ie, frame shift mutations).
  • Prior endocrine therapy for breast cancer within the last 2 years
  • Women who are pregnant, are planning to become pregnant, or are breast-feeding
  • Any investigational treatment for the current diagnosis of breast cancer
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  • HER2 amplification by FISH (HER2:CEP17 ratio >2.0) or IHC (HER2 (3+)
  • Hepatic function impairment as defined by AST or ALT > 3x ULN OR total serum bilirubin > 1.5 (in patients with known Gilbert syndrome, a total bilirubin of > 3.0 x ULN or direct bilirubin > 1.5 x ULN)
  • Significant chronic gastrointestinal disorder with diarrhea as a major symptom (eg, Crohn's disease, malabsorption, or Grade ≥2 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events Version 4.0 [CTCAE version 4.0] diarrhea of any etiology at baseline.
  • Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness/social situations that could, in the Investigator's judgment, make the patient inappropriate for this study.
  • Known hypersensitivity to any component of the investigational product, required combination therapy, or loperamide.
  • Unable or unwilling to swallow tablets.
  • Unable or unwilling to complete study procedures such as research biopsies or imaging
  • Any medical condition that in the judgement of the co-investigator would impair the patient's ability to complete the planned study therapy

Trial locations and contacts

5 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Vanderbilt-Ingram Services for Timely Access contact

800-811-8480

cip@vumc.org

5 sites in 1 country

United States5 sites, 5 recruiting
  • Emory University/ Winship Cancer Institute

    Atlanta, Georgia, 30322

    Kevin Kalinsky, MD

    Not yet recruiting
  • University of Texas, Southwestern

    Dallas, Texas, 75390

    Nisha Unni, Nisha.Unni@UTSouthwestern.edu

    Carlos Arteaga, MD

    Recruiting
  • Baylor College of Medicine

    Houston, Texas, 77030

    Bora Lim, MD

    Not yet recruiting
  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37203

    Vanderbilt-Ingram Service for Timely Access, 800-811-8480, cip@vumc.org

    Laura Kennedy, MD, PhD

    Recruiting
  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

    Adam Brufsky, MD

    Not yet recruiting

Other trials in United States

About this study

This phase II trial tests how well neratinib prior to the primary treatment (neoadjuvant) works in treating patients with stage I-III HER2 mutated lobular breast cancers. Neratinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving neratinib in addition to normal therapy may work better in treating cancer than the endocrine therapy patients would normally receive.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Determine efficacy of neoadjuvant neratinib in combination with endocrine therapy.

SECONDARY OBJECTIVES:

  1. Determine additional efficacy outcomes of neoadjuvant neratinib in combination with endocrine therapy.

II. Compare the safety and tolerability of neratinib plus endocrine therapy.

CORRELATIVE OBJECTIVE:

  1. Establish HER2-mutant invasive lobular carcinoma (ILC) organoids.

OUTLINE: Patients are randomized to 1 of 2 treatments.

TREATMENT A: Patients receive standard of care endocrine therapy over 4 weeks for 1 cycle. Patients undergo breast tissue biopsy during the lead-in window/cycle 1. Patients then endocrine therapy and neratinib orally (PO) daily for 20 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo breast surgery during weeks 24-25. Patients undergo collection of blood samples every 4 weeks while on treatment, at weeks 4 and 24, and at time of surgery. Patients undergo mammogram, ultrasound, or breast magnetic resonance imaging (MRI) prior to surgery.

TREATMENT B: Patients receive standard of care endocrine therapy and neratinib PO over 4 weeks for 1 cycle. Patients undergo breast tissue biopsy during the lead-in window/cycle 1. Patients then continue endocrine therapy and neratinib PO daily for 20 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo breast surgery during weeks 24-25. Patients undergo collection of blood samples every 4 weeks while on treatment, at weeks 4 and 24, and at time of surgery. Patients undergo mammogram, ultrasound, or breast MRI prior to surgery.

After completion of study treatment, patients are followed up for 4 weeks after study drugs interruption.

Being tested
Endocrine Therapy, Biopsy of breast, Neratinib, Biospecimen Collection, Mammogram
Medical subject headings
Carcinoma, Lobular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Endocrine TherapyProcedure or surgery

    Undergo endocrine therapy

  • Biopsy of breastProcedure or surgery

    Undergo breast biopsy

  • NeratinibDrug

    Taken by mouth

  • Biospecimen CollectionProcedure or surgery

    Undergo collection of blood samples

  • MammogramProcedure or surgery

    Undergo Mammogram

  • Magnetic Resonance ImagingProcedure or surgery

    Undergo breast Magnetic Resonance Imaging

  • Breast SurgeryProcedure or surgery

    Undergo Breast Surgery

  • UltrasoundProcedure or surgery

    Undergo Ultrasound

Study groups in NCT05919108
Study groupRoleWhat they receive
Treatment A (endocrine therapy)Active comparatorPatients receive standard of care endocrine therapy over 4 weeks for 1 cycle. Patients undergo breast tissue biopsy during the lead-in window/cycle 1. Patients then endocrine therapy and neratinib PO daily for 20 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo breast surgery during weeks 24-25. Patients undergo collection of blood samples every 4 weeks while on treatment, at weeks 4 and 24, and at time of surgery. Patients undergo mammogram, ultrasound, or breast MRI prior to surgery.
Receives: Procedure: Endocrine Therapy; Procedure: Biopsy of breast; Drug: Neratinib; Procedure: Biospecimen Collection; Procedure: Mammogram; Procedure: Magnetic Resonance Imaging; Procedure: Breast Surgery
Treatment B (endocrine therapy, neratinib)ExperimentalPatients receive standard of care endocrine therapy and neratinib PO over 4 weeks for 1 cycle. Patients undergo breast tissue biopsy during the lead-in window/cycle 1. Patients then continue endocrine therapy and neratinib PO daily for 20 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo breast surgery during weeks 24-25. Patients undergo collection of blood samples every 4 weeks while on treatment, at weeks 4 and 24, and at time of surgery. Patients undergo mammogram, ultrasound, or breast MRI prior to surgery.
Receives: Procedure: Endocrine Therapy; Procedure: Biopsy of breast; Drug: Neratinib; Procedure: Biospecimen Collection; Procedure: Mammogram; Procedure: Magnetic Resonance Imaging; Procedure: Breast Surgery; Procedure: Ultrasound

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Preoperative endocrine prognostic index score

    Measured: Up to 5 years

Secondary outcomes (5)
  1. Pathological complete response rate

    Will be summarized for the entire cohort by response.

    Measured: Up to 5 years

  2. Change in Ki67

    Measured: At 4 weeks

  3. Residual cancer burden index

    Will be summarized for the entire cohort by response

    Measured: Up to 5 years

  4. Rates of breast conservation therapy

    Will be summarized for the entire cohort by response

    Measured: Up to 5 years

  5. Incidence of adverse events (NCI Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0)

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jun 2023
  2. Study start11 Jun 2024
  3. Primary completion30 Apr 2030 (estimated)
  4. Study completion30 Apr 2031 (estimated)

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05919108
Sponsor's protocol ID
VICC-NCBRE23172
Other IDs
NCI-2023-04468, 1R01CA273246-01A1
Status last verified
Aug 2026
First submitted
15 Jun 2023
Last updated
19 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Endocrine Therapy, Biopsy of breast and Neratinib in people with Anatomic Stage I Breast Cancer and Anatomic Stage II Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 5 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 24 inclusion and 14 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 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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 Vanderbilt-Ingram Services for Timely Access (800-811-8480, cip@vumc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Preoperative endocrine prognostic index score (time frame: Up to 5 years). 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 19 Aug 2026; AzTrials last refreshed its copy on 6 Nov 2026.

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