RECRUITING

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

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Conditions

Anatomic Stage I Breast CancerAnatomic Stage II Breast CancerAnatomic Stage III Breast CancerInvasive Breast Lobular Carcinoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2025-01-31
Study Completion:2031-04-30
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05919108

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Subjects aged 18 years or older at signing of informed consent.
  2. * New diagnosis of clinical stage I-III HR+ histologically-proven (i.e. absent or decreased e-cadherin expression) invasive lobular carcinoma
  3. * Synchronous breast tumors are permitted as long as the synchronous tumor is ER+ and HER2-negative.
  4. * 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)
  5. * 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.
  6. * Archival tissue availability (if not available a fresh tumor biopsy will be required) and subject must agree to submission of sample for central testing
  7. * Minimum tumor size of ≥1.5 cm by US, mammogram, MRI imaging, or clinical breast exam
  8. * ECOG performance status 0 or 1
  9. * Patients must have adequate hematologic, hepatic, and renal function. All laboratory tests must be obtained within 1 month of study entry. This includes:
  10. * Estimated glomerular filtration rate of ≥50 mL/min
  11. * Albumin ≥ 2.5 g/dL
  12. * ANC ≥1500/mm\^3
  13. * Platelet count ≥100,000/mm\^3
  14. * HgB ≥ 9 g/dL
  15. * 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)
  16. * AST and ALT ≤ 3 x ULN
  17. * Pre-, peri-, or post-menopausal, confirmed by history or laboratory testing as needed
  18. * Diagnostic biopsy tissue availability with sufficient tumor to permit NGS (if not available, a fresh biopsy will be required)
  19. * No prior treatment for current diagnosis of breast cancer
  20. * 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:
  21. * Age ≥ 55 years
  22. * 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.
  1. * Evidence of distant metastatic disease
  2. * Synchronous breast cancer that is estrogen receptor negative OR HER2-amplified OR requires treatment with neoadjuvant chemotherapy per the judgement of the treating physician
  3. * 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).
  4. * Prior endocrine therapy for breast cancer within the last 2 years
  5. * Women who are pregnant, are planning to become pregnant, or are breast-feeding
  6. * Any investigational treatment for the current diagnosis of breast cancer
  7. * HER2 amplification by FISH (HER2:CEP17 ratio \>2.0) or IHC (HER2 (3+)
  8. * 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)
  9. * 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.
  10. * 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.
  11. * Known hypersensitivity to any component of the investigational product, required combination therapy, or loperamide.
  12. * Unable or unwilling to swallow tablets.
  13. * Unable or unwilling to complete study procedures such as research biopsies or imaging
  14. * Any medical condition that in the judgement of the co-investigator would impair the patient's ability to complete the planned study therapy

Contacts and Locations

Study Contact

Vanderbilt-Ingram Services for Timely Access
CONTACT
800-811-8480
cip@vumc.org

Principal Investigator

Laura Kennedy, MD, PhD
PRINCIPAL_INVESTIGATOR
Vanderbilt University/Ingram Cancer Center

Study Locations (Sites)

Emory University/ Winship Cancer Institute
Atlanta, Georgia, 30322
United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37203
United States
University of Texas, Southwestern
Dallas, Texas, 75390
United States
Baylor College of Medicine
Houston, Texas, 77030
United States

Collaborators and Investigators

Sponsor: Vanderbilt-Ingram Cancer Center

  • Laura Kennedy, MD, PhD, PRINCIPAL_INVESTIGATOR, Vanderbilt University/Ingram Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-01-31
Study Completion Date2031-04-30

Study Record Updates

Study Start Date2025-01-31
Study Completion Date2031-04-30

Terms related to this study

Additional Relevant MeSH Terms

  • Anatomic Stage I Breast Cancer
  • Anatomic Stage II Breast Cancer
  • Anatomic Stage III Breast Cancer
  • Invasive Breast Lobular Carcinoma