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

NCT03812393 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: 2018-002
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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)

Conditions

Triple Negative Breast Cancer; Early-stage Breast Cancer; HER2-positive Breast Cancer

Outcome Measures

Primary Outcomes (2)

• The percentage of patients experiencing ≥ 20% response to neratinib only therapy

  patient with HER2 positive signal by CELx will be exposed to neratinib to determine response to HER2 therapy

  4 weeks

• rate of pathologic complete response (pCR)

  percentage of patients with no tumor in breast at surgery following study treatment

  15 weeks

Secondary Outcomes (5)

• Clinical complete response (cCR)

  15 weeks

• Residual cancer burden (RCB) 0-1

  15 weeks

• 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

• Safety and Toxicity per NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).

  15 weeks

• Increase in the number of patients completing neratinib prescription with the use of web based symptom monitoring

  15 weeks

Study Arms (1)

Treatment

EXPERIMENTAL

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

Drug: Neratinib

Interventions

Neratinib DRUG

For cycle 1 subjects will receive Neratinib 240mg daily for 21 days. For cycle 2-5, subjects will receive carboplatin AUC of 1.5 and Paclitaxel 80mg/m2 on day one in combination with Neratinib 240mg daily for 21 day.

Also known as: Live Cell HER2 signaling Transduction Analysis (CELx)

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• West Cancer Center: lead
• Celcuity Inc: collaborator
• Puma Biotechnology, Inc.: collaborator

Study Sites (1)

West Cancer Center

Germantown, Tennessee, 38139, United States

Location

Related Publications (2)

• Huang Y, Burns DJ, Rich BE, MacNeil IA, Dandapat A, Soltani SM, Myhre S, Sullivan BF, Furcht LT, Lange CA, Hurvitz SA, Laing LG. A functional signal profiling test for identifying a subset of HER2-negative breast cancers with abnormally amplified HER2 signaling activity. Oncotarget. 2016 Nov 29;7(48):78577-78590. doi: 10.18632/oncotarget.12480.

  PMID: 27713176 RESULT

• Huang Y, Burns DJ, Rich BE, MacNeil IA, Dandapat A, Soltani SM, Myhre S, Sullivan BF, Lange CA, Furcht LT, Laing LG. Development of a test that measures real-time HER2 signaling function in live breast cancer cell lines and primary cells. BMC Cancer. 2017 Mar 16;17(1):199. doi: 10.1186/s12885-017-3181-0.

  PMID: 28302091 RESULT

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

neratinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Gregory A Vidal, MD.,PhD

  West Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: single-arm interventional clinical trial with an early check for futility using a surrogate endpoint

Study Record Dates

• First Submitted: January 8, 2019
• First Posted: January 23, 2019
• Study Start: June 21, 2019
• Primary Completion: December 15, 2024
• Study Completion: December 15, 2024
• Last Updated: December 18, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)