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

Plain English Summary

Trial of Pre-operative Neratinib and Endocrine Therapy With Trastuzumab in ER-Positive, HER-2 Positive Breast Cancers is a Phase 2 clinical trial sponsored by Ruth O'Regan studying Breast Cancer, HER2-positive Breast Cancer, ER Positive Breast Cancer, PR-Positive Breast Cancer. This trial tests a combination of drugs (neratinib, endocrine therapy, and trastuzumab) given before surgery to shrink HER2-positive breast tumors. It is for postmenopausal women with early-stage (Stage I-III) HER2-positive and ER-positive breast cancer that can be removed by surgery. Participants will take study drugs for about 24 weeks before surgery, and may have biopsies to check the tumor's response. After surgery, they will receive standard treatment. Alternatives include standard neoadjuvant (pre-surgery) chemotherapy or endocrine therapy, depending on the cancer's specific characteristics. The trial aims to enroll 30 participants.

Official 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. Following surgery, patients will receive standard of care HER2-directed and endocrine therapy at the treating physician's discretion.

Who Can Participate

Here is what you need to know about eligibility for this trial. Women aged 18 or older who have gone through menopause. Must have early-stage (Stage I-III) invasive breast cancer that is both HER2-positive and ER-positive, and is small enough for surgery. Cannot have cancer that has spread to distant parts of the body or is locally advanced (Stage IIIC or greater). Must have adequate organ function (heart, kidney, liver, blood counts) and be able to swallow pills. This trial is studying Breast Cancer, HER2-positive Breast Cancer, ER Positive Breast Cancer, PR-Positive Breast Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The main goal is to see if the pre-surgery treatment can completely eliminate invasive cancer cells in the breast and lymph nodes, meaning the surgery is more likely to be successful and the cancer is The specific primary outcome measures are: Pathologic Complete Response (pCR) (24 weeks). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to improve treatment outcomes for a specific type of early-stage breast cancer by using a novel pre-surgery drug combination to potentially reduce tumor size and improve the chances of Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Breast Cancer, HER2-positive Breast Cancer, ER Positive Breast Cancer, PR-Positive Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial targets a significant market of HER2-positive breast cancer patients, with a competitive landscape focused on novel therapies that improve outcomes. Success could lead to a new standard of Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this pre-surgery treatment is right for you and how it might affect your surgery and recovery. Be prepared for regular clinic visits for drug administration, blood tests, and biopsies to monitor your response to treatment. You will need to take study medications daily for about 24 weeks before your surgery. This trial is currently recruiting participants. The trial is being conducted at 4 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 30 participants

Interventions

• DRUG: Neratinib — 120mg for 7 days; 160mg for 7 days ; 240mg for 7 days. 240 mg (up to a maximum of 24 weeks) orally daily\*.
• DRUG: Letrozole (L) or Anastrozole (A) — L: (2.5 mg) OR A: (1 mg) orally daily (up to a maximum of 24 weeks)\*
• DRUG: Trastuzumab — 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.

Primary Outcomes

• Pathologic Complete Response (pCR) (24 weeks)

Secondary Outcomes

• Assess Adverse Events (24 weeks)
• Pathological Complete Response (pCR) (24 weeks)
• Measure Residual Disease (24 weeks)

Full Eligibility Criteria

Inclusion Criteria:

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
* 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.

Exclusion Criteria:

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).
* 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 fai

Trial Locations

• University of Illinois Cancer Center, Chicago, Illinois, United States
• University of Rochester Medical Center, Rochester, New York, United States
• Penn State Cancer Institute, Hershey, Pennsylvania, United States
• University of Wisconsin, Madison, Wisconsin, United States

Frequently Asked Questions

Related Conditions

• Breast Cancer
• HER2-positive Breast Cancer
• ER-positive Breast Cancer
• PR-positive Breast Cancer
• Hormone Receptor-positive Breast Cancer
• Early-stage Breast Cancer
• Invasive Breast Cancer
• Oncology
• Medical Oncology
• Women's Health

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