Phase II Trial Evaluating the Efficacy and Safety of Neoadjuvant Neratinib and Chemotherapy in Early Stage Triple-Negative Breast Cancer Patients Who Exhibit Enhanced HER2 Signaling by Live Cell HER2 Signaling Transduction Analysis (FACT-2)
Overview
- Phase
- Phase 2
- Intervention
- Neratinib
- Conditions
- Triple Negative Breast Cancer
- Sponsor
- West Cancer Center
- Enrollment
- 27
- Locations
- 1
- Primary Endpoint
- rate of pathologic complete response (pCR)
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
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 Patients Who Exhibit Enhanced HER2 Signaling by Live Cell HER2 Signaling Transduction Analysis (FACT-2)
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-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.
Investigators
Eligibility 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
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.
Arms & Interventions
Treatment
TNBC patients with HER2 signal positive are treated with neratinib for 3 weeks followed by 12 weeks of neratinib in combination with weekly paclitaxel and carboplatin
Intervention: Neratinib
Outcomes
Primary Outcomes
rate of pathologic complete response (pCR)
Time Frame: 15 weeks
percentage of patients with no tumor in breast at surgery following study treatment
The percentage of patients experiencing ≥ 20% response to neratinib only therapy
Time Frame: 4 weeks
patient with HER2 positive signal by CELx will be exposed to neratinib to determine response to HER2 therapy
Secondary Outcomes
- The PCR rate in patients experiencing greater than or equal to 20% reduction in tumor volume following treatment with neratinib only in cycle 1.(15 weeks)
- Clinical complete response (cCR)(15 weeks)
- Residual cancer burden (RCB) 0-1(15 weeks)
- Increase in the number of patients completing neratinib prescription with the use of web based symptom monitoring(15 weeks)
- Safety and Toxicity per NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).(15 weeks)