Study of Neoadjuvant Chemotherapy Plus Trastuzumab and Pertuzumab in HER2-Negative Breast Cancer Patients With Abnormal HER2 Signaling

  • STATUS
    Recruiting
  • End date
    Mar 30, 2022
  • participants needed
    64
  • sponsor
    NSABP Foundation Inc
Updated on 21 April 2021
Investigator
Director, Department of Site and Study Management
Primary Contact
Cancer Care Specialists of Central Illinois (1.5 mi away) Contact
+41 other location
platelet count
paclitaxel
cancer
cyclophosphamide
progesterone
doxorubicin
probe
metastasis
neutrophil count
immunohistochemistry
HER2
bone scan
adenocarcinoma
progesterone receptor
invasive breast cancer
core needle biopsy
pet-ct scan

Summary

This is a prospective, single arm, open label, multicenter interventional study designed to evaluate the efficacy of neoadjuvant chemotherapy with anti-HER2 antibodies in patients with HER2-negative invasive breast cancer who have abnormal HER2 signaling activity determined by the Celcuity CELx HER2 Signaling Function (HSF) testing.

Description

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 signaling activity (abnormally or normally active).

Patients who have abnormal HER2 signaling activity will receive weekly paclitaxel plus the anti-HER2 therapy regimen of trastuzumab and pertuzumab following completion of initial doxorubicin/cyclophosphamide.The primary endpoint of the study is to evaluate whether patients with HER2-negative breast cancers based on standard American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) testing criteria, but with abnormal HER2-driven signaling pathways determined by the Celcuity HSF assay and receive HER2-targeted therapy with neoadjuvant chemotherapy, will have a higher rate of pathological complete response in the breast and lymph nodes (pCR breast and lymph nodes) than has been found historically in patients with HER2-negative breast cancer who have received neoadjuvant chemotherapy alone. 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 270 patients will need to be prescreened in order to enroll 54 patients (26 ER-positive/HER2-negative and 28 ER-negative/HER2-negative) who have abnormal HER2 signaling activity.

Details
Condition HER2 Negative Breast Cancer
Treatment cyclophosphamide, Trastuzumab, doxorubicin, Pertuzumab, Weekly paclitaxel, Celcuity CELx HSF
Clinical Study IdentifierNCT03412643
SponsorNSABP Foundation Inc
Last Modified on21 April 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

SCREENING PRIOR TO INITIATING CHEMOTHERAPY
Patient must have an Eastern Cooperative Oncology Group (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 greater than or equal
0 cm on physical exam
The regional lymph nodes can be cN0, cN1, or cN2a
Histological grade II or III tumor
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 ER and progesterone
receptor (PgR) analysis assessed by current ASCO/CAP Guidelines. Patients are
eligible with either hormone receptor-positive or hormone receptor-negative
tumors
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 in situ hybridization (ISH) non-amplified with a ratio of HER2 to chromosome enumeration probe 17 (CEP17) less than 2.0, and if reported, average HER2 gene copy number less than 4 signals/cells; or
ISH non-amplified with a ratio of HER2 to CEP17 less than 2.0, and if reported, average HER2 gene copy number less than 4 signals/cells
Blood counts performed within 6 weeks prior to initiating chemotherapy must
meet the following criteria
absolute neutrophil count (ANC) must be greater than or equal 1200/mm3
platelet count must be greater than or equal 100,000/mm3; and
hemoglobin must be greater than or equal 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 less than or equal to upper limit of normal (ULN) for the lab unless the patient has a bilirubin elevation greater than ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and
alkaline phosphatase must be less than or equal to 2.5 x ULN for the lab; and
aspartate aminotransferase (AST) must be less than or equal to 1.5 x ULN for the lab
Alkaline phosphatase and AST may not both be greater than the ULN. For example, if the alkaline phosphatase is greater than the ULN but less than or equal to 2.5 x ULN, the AST must be less than or equal to the ULN. If the AST is greater than the ULN but less than or equal to 1.5 x ULN, the alkaline phosphatase must be less than or equal to ULN. Note: If alanine aminotransferase (ALT) is performed instead of AST (per institution's standard practice), the ALT value must be less than or equal to 1.5 x ULN; if both were performed, the AST must be less than or equal to 1.5 x ULN
Patients with AST or alkaline phosphatase greater than 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 next criteria are met
Patients with alkaline phosphatase that is greater than ULN but less than or
equal to 2.5 x ULN or unexplained bone pain are eligible for inclusion in the
study if a bone scan, PET-CT scan, or positron emission tomography (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 less than or equal to 1.5 x ULN for the lab
The left ventricular ejection fraction (LVEF) assessment by echocardiogram or
multi-gated acquisition (MUGA) scan performed within 90 days prior to
initiating chemotherapy must be greater than or equal 55 percent 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
MAIN STUDY ENROLLMENT
Tumor determined to have abnormal HER2-driven signaling activity based on the
CELx HSF test

Exclusion Criteria

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 ductal carcinoma in situ [DCIS] or lobular
carcinoma in situ [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
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 greater than 150
mmHg or diastolic BP greater than 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) greater than or equal to 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 greater than or
equal to 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
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