Evaluating the Efficacy of Neratinib on Live Cell HER2 Signaling Transduction Analysis Positive Triple Negative Breast

  • End date
    Apr 15, 2023
  • participants needed
  • sponsor
    West Cancer Center
Updated on 25 January 2021
ct scan
platelet count
ejection fraction
breast cancer
gilbert's syndrome
neutrophil count
triple-negative breast cancer
adenocarcinoma of the breast
core needle biopsy
multifocal breast cancer


An Open-Label Phase II Trial to Evaluate the Efficacy and Safety of Neoadjuvant Neratinib Followed by Weekly Paclitaxel and Carboplatin Plus Neratinib in Early Stage Triple-Negative Breast Cancer Patients Who Exhibit Enhanced HER2 Signaling by Live Cell HER2 Signaling Transduction Analysis (FACT-2)


This is a prospective, single arm, open label, interventional study designed to evaluate the efficacy of neoadjuvant chemotherapy with a pan-HER inhibitor in patients with ER-/PR-/HER2-(triple-negative) invasive breast cancer who have abnormal HER2-driven signaling activity determined by the Celcuity CELx HER2 signal function (HSF) test. Patients will be required to have a prescreening research core needle biopsy to procure a fresh tumor specimen that will be sent to Celcuity for CELx HSF testing, in order to assess the status of their HER2-driven signaling activity (abnormally or normally active). While waiting for results of the CELx HSF test, patients may receive the first dose of weekly paclitaxel at the investigator's discretion. Patients whose CELx HSF test indicate they have abnormal HER2-driven signaling activity will then receive neratinib as a single agent daily for 21 days and then neratinib plus paclitaxel and carboplatin.

The primary endpoint of the study is to evaluate whether patients with triple-negative breast cancers (estrogen (ER) and progesterone (PR) receptors < 10%; HER2-negative per standard ASCO/CAP testing criteria), but with abnormal HER2-driven signaling pathways determined by the Celcuity CELx HSF assay, and who receive HER2-targeted therapy with neoadjuvant chemotherapy will have a higher rate of pathological complete response (pCR) in the breast and lymph nodes (pCR breast and lymph nodes) than has been found historically in patients with triple-negative breast cancer who have received neoadjuvant chemotherapy. Secondary endpoints include pathologic complete response (breast), clinical complete response (cCR), residual cancer burden (RCB) 0-1 index, and relationship between quantitative CELx score and pCR rate.

It is expected that approximately 135 patients will need to be prescreened in order to enroll 27 patients who have abnormal HER2-driven signaling activity.

Condition Breast Cancer, Breast Cancer, Diet and Nutrition, Chronic Diarrhea, Skin Wounds, Chronic Shoulder Pain, Vaginal Atrophy, Adverse Effects, Drugs, Injection Port, Breast Cancer - HER2 Positive, Anal Dysplasia, Primary Immunodeficiency, Pediatric Health, Near-Sighted Corrective Surgery, HER2 Positive Breast Cancer, Peripheral Arterial Occlusive Disease, Triple Negative Breast Cancer, Brain Function, Early Stage Breast Cancer, Recurrent Respiratory Papillomatosis, Razor Bumps (Pseudofolliculitis Barbae), Metastatic Triple-Negative Breast Cancer, her2/neu-positive breast cancer, her2-positive breast cancer
Treatment Neratinib
Clinical Study IdentifierNCT03812393
SponsorWest Cancer Center
Last Modified on25 January 2021


Yes No Not Sure

Inclusion Criteria

The patient must have consented to participate and must have signed and dated an appropriate IRB-approved consent form that conforms to federal and i institutional guidelines for the pre-entry research core biopsy for CELx HSF testing and for initiating chemotherapy
Patients must be female
Patients must be 18 years old
Patient must have an ECOG performance status of 0 or 1
The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy
The primary breast tumor must be palpable and measure 1.0 cm on physical exam
The regional lymph nodes can be cN0 or cN1
The tumor size can be T1c or T2
Ipsilateral axillary lymph nodes must be evaluated by imaging (mammogram, ultrasound, and/or MRI) within 6 weeks prior to initiating chemotherapy. If suspicious or abnormal, FNA or core biopsy is recommended, also within 6 weeks prior to initiating chemotherapy. Findings of these evaluations will be used to determine the nodal status prior to initiating chemotherapy
Nodal status - negative
Imaging of the axilla is negative
Imaging is suspicious or abnormal but the FNA or core biopsy of the questionable node(s) on imaging is negative
Nodal status - positive
FNA or core biopsy of the node(s) is cytologically or histologically suspicious or positive
Imaging is suspicious or abnormal but FNA or core biopsy was not performed
Tumor specimen obtained at the time of diagnosis must have estrogen (ER) and progesterone (PR) receptors < 10%
Tumor specimen obtained at the time of diagnosis must have been determined to be HER2-negative as follows
Immunohistochemistry (IHC) 0-1+; or
IHC 2+ and ISH non-amplified with a ratio of HER2 to CEP17 < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells; or
ISH non-amplified with a ratio of HER2 to CEP17 < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells
Blood counts performed within 6 weeks prior to initiating chemotherapy must meet the following criteria
Absolute neutrophil count (ANC) must be 1200/mm3
platelet count must be 100,000/mm3; and
hemoglobin must be 10 g/dL
The following criteria for evidence of adequate hepatic function performed within 6 weeks prior to initiating chemotherapy must be met
total bilirubin must be upper limit of normal (ULN) for the lab unless the patient has a bilirubin elevation > ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and
alkaline phosphatase must be 2.5 x ULN for the lab; and
AST must be 1.5 x ULN for the lab
Alkaline phosphatase and AST may not both be > the ULN. For example, if the alkaline phosphatase is > the ULN but 2.5 x ULN, the AST must be the ULN. If the AST is > the ULN but 1.5 x ULN, the alkaline phosphatase must be ULN. Note: If ALT is performed instead of AST (per institution's standard practice), the ALT value must be 1.5 x ULN; if both were performed, the AST must be 1.5 x ULN
Patients with AST or alkaline phosphatase > ULN are eligible for inclusion in the study if liver imaging (CT, MRI, PET-CT, or PET scan) performed within 6 weeks prior to initiating chemotherapy does not demonstrate metastatic disease and the requirements in criterion 4.2.13 are met
Patients with alkaline phosphatase that is > ULN but 2.5 x ULN or unexplained bone pain are eligible for inclusion in the study if a bone scan, PET-CT scan, or PET scan performed within 6 weeks prior to initiating chemotherapy does not demonstrate metastatic disease
Serum creatinine performed within 6 weeks prior to initiating chemotherapy must be 1.5 x ULN for the lab
The left ventricular ejection fraction (LVEF) assessment by echocardiogram or MUGA scan performed within 90 days prior to initiating chemotherapy must be 50% regardless of the facility's lower limit of normal (LLN)
Patients with reproductive potential must agree to use an effective non-hormonal method of contraception during therapy, and for at least 7 months after the last dose of study therapy
Patients are candidates for weekly paclitaxel and carboplatin chemotherapy as determined by treating physician
Patients with multifocal breast cancer are included as long as none of the tumors are HER2 positive by IHC or FISH and targeted lesion meets current inclusion criteria
Conditions for patient eligibility (Study Enrollment) A patient cannot be considered eligible for this study unless all of the following conditions are met
The patient must have consented to participate and must have signed and dated an appropriate IRB-approved consent form that conforms to federal and institutional guidelines for the FACT-2 study treatment
Tumor determined to have abnormal HER2-driven signaling activity based on the CELx HSF test

Exclusion Criteria

T3 or T4 tumors including inflammatory breast cancer
FNA alone to diagnose the breast cancer
Excisional biopsy or lumpectomy performed prior to initiating chemotherapy
Surgical axillary staging procedure prior to initiating chemotherapy. Pre- neoadjuvant therapy sentinel node biopsy is not permitted. (FNA or core biopsy is acceptable.)
Definitive clinical or radiologic evidence of metastatic disease. Required imaging studies must have been performed within 6 weeks prior to initiating chemotherapy
Synchronous bilateral invasive breast cancer. (Patients with synchronous and/or previous contralateral DCIS or LCIS are eligible.)
Any previous history of ipsilateral invasive breast cancer or ipsilateral DCIS. (Patients with synchronous or previous ipsilateral LCIS are eligible.)
Previous therapy with anthracycline, taxanes, trastuzumab, or other HER2 targeted therapies for any malignancy
Any sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy, etc. (These patients are eligible if this therapy is discontinued prior to initiating chemotherapy.)
History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 2 years prior to initiating chemotherapy
Cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens. This includes but is not confined to
Active cardiac disease
angina pectoris that requires the use of anti-anginal medication
ventricular arrhythmias except for benign premature ventricular contractions
supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
conduction abnormality requiring a pacemaker
valvular disease with documented compromise in cardiac function; and
symptomatic pericarditis
History of cardiac disease
myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular (LV) function
history of documented congestive heart failure (CHF); and
documented cardiomyopathy
Uncontrolled hypertension defined as sustained systolic BP > 150 mmHg or diastolic BP > 90 mmHg. (Patients with initial BP elevations are eligible prior to initiating chemotherapy if initiation or adjustment of BP medication lowers pressure.)
Active hepatitis B or hepatitis C with abnormal liver function tests
Intrinsic lung disease resulting in dyspnea
Poorly controlled diabetes mellitus
Active infection or chronic infection requiring chronic suppressive antibiotics
Patients known to be HIV positive
Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory neuropathy) grade 2, per the CTCAE v4.0
Malabsorption syndrome, ulcerative colitis, resection of the stomach or small bowel, or other disease significantly affecting gastrointestinal function
Other non-malignant systemic disease that would preclude treatment with any of the treatment regimens or would prevent required follow-up
Conditions that would prohibit administration of corticosteroids
Chronic daily treatment with corticosteroids with a dose of 10 mg/day methylprednisolone equivalent (excluding inhaled steroids)
Known hypersensitivity to any of the study drugs or any of the ingredients or excipients of these drugs (e.g., Cremophor EL), including sensitivity to benzyl alcohol
Pregnancy or lactation at the initiation of chemotherapy. (Note: Pregnancy testing must be performed within 2 weeks prior to initiating chemotherapy according to institutional standards for women of childbearing potential)
Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements
Evidence after a clinical examination that the subject's tumor is progressing after treatment with one week of paclitaxel and before a CELx HSF test result is available
For participation in adherence monitoring: no access to the web via smart phone, tablet or computer
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