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Status:

UNKNOWN

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

Lead Sponsor:

West Cancer Center

Collaborating Sponsors:

Celcuity Inc

Puma Biotechnology, Inc.

Conditions:

Triple Negative Breast Cancer

Early-stage Breast Cancer

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief 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 Pati...

Detailed Description

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-negativ...

Eligibility Criteria

Inclusion

  • 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

  • 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

Key Trial Info

Start Date :

June 21 2019

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

December 15 2024

Estimated Enrollment :

27 Patients enrolled

Trial Details

Trial ID

NCT03812393

Start Date

June 21 2019

End Date

December 15 2024

Last Update

December 18 2023

Active Locations (1)

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West Cancer Center

Germantown, Tennessee, United States, 38139