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

• Status: Recruiting
• Trial end date: 2023-04-15
• Target enrollment: 0
• Participant gender: All

Summary

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)

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: West Cancer Center
• Collaborators: Celcuity; Celcuity, Inc.; Puma Biotechnology, Inc.

Criteria

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