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

NCT03412643 | Unknown Phase 2 FDA Drug FDA Device

• 1 other identifier: NSABP FB-12
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 43

Brief 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.

Conditions

HER2-negative Breast Cancer

Keywords

NSABP; Celcuity; HER2-negative; invasive; breast cancer; Open-label; Neoadjuvant; Early stage; Doxorubicin; Cyclophosphamide; Paclitaxel; Trastuzumab; Pertuzumab; CELx HSF; HER2 Signaling Function test; anti-HER2 Antibodies

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response (PCR) to study therapy (both breast and lymph node-combined; ypT0/Tis ypN0)

  Percentage of patients with absence of residual invasive cancer in H\&E slides of resected breast specimens and all sampled regional lymph nodes following the completion of neoadjuvant systemic therapy

  From initiation of study therapy to time of surgery, which is usually performed 3 to 4 weeks after completion of study therapy

Secondary Outcomes (5)

• Pathologic complete response to study therapy (breast)

  From initiation of study therapy to time of surgery, which is usually performed 3 to 4 weeks after completion of study therapy

• Clinical complete response (both breast and axilla)

  From initiation of study therapy to 2-4 weeks after completion of study therapy

• Residual cancer burden (RCB)

  From initiation of study therapy to time of surgery, which is usually performed 3 to 4 weeks after completion of study therapy

• Logistic regression

  From prior to study entry (time of CELx score assay) to 4-6 weeks after surgery (pCR outcome determination)

• Frequency of adverse events assessed by CTCAE 4.0

  From beginning of study therapy to 4-6 weeks after surgery

Study Arms (1)

Arm 1

EXPERIMENTAL

Celcuity CELx HSF Test on tumor material obtained from research core biopsy to select patients with abnormal HER2 signaling tumors Doxorubicin + cyclophosphamide followed by Weekly Paclitaxel +Trastuzumab+Pertuzumab

Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Weekly Paclitaxel; Drug: Trastuzumab; Drug: Pertuzumab; Diagnostic Test: Celcuity CELx HSF

Interventions

Doxorubicin DRUG

60 mg/m2 IV Day 1 every 2 weeks or 3 weeks at investigator's discretion for a total of 4 cycles

Arm 1

Cyclophosphamide DRUG

600 mg/m2 IV Day 1 every 2 weeks or 3 weeks at investigator's discretion for a total of 4 cycles

Arm 1

Weekly Paclitaxel DRUG

80 mg/m2 IV weekly for 12 doses

Arm 1

Trastuzumab DRUG

loading dose of 8 mg/kg IV; then 6 mg/kg IV every 3 weeks for Cycles 2-4

Arm 1

Pertuzumab DRUG

loading dose of 840 mg IV; then 420 mg IV every 3 weeks for Cycles 2-4

Arm 1

Celcuity CELx HSF DIAGNOSTIC_TEST

Prior to drug interventions 3, 4,and 5, the Celcuity CELx HSF diagnostic test will be conducted to assess HER2 signaling activity

Arm 1

Eligibility Criteria

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

You may qualify if:

• 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 2.0 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;

You may not qualify if:

• 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 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 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.

Sponsors & Collaborators

• NSABP Foundation Inc: lead
• Celcuity, LLC: collaborator
• Genentech, Inc.: collaborator

Study Sites (43)

Arrowhead Regional Medical Center

Colton, California, 92324, United States

RECRUITING

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

RECRUITING

University of Florida Cancer Center at Orlando Health

Orlando, Florida, 32806, United States

RECRUITING

Cancer Care Specialists of Central Illinois

Decatur, Illinois, 62526, United States

RECRUITING

Edward Hospital Cancer Center

Naperville, Illinois, 60540-7499, United States

RECRUITING

Fort Wayne Medical Oncology and Hematology, Inc.

Fort Wayne, Indiana, 46804, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

University of Louisville JG Brown Cancer Center

Louisville, Kentucky, 40202, United States

RECRUITING

University Medical Center New Orleans

New Orleans, Louisiana, 70112, United States

RECRUITING

Greater Baltimore Medical Center

Baltimore, Maryland, 21204, United States

RECRUITING

St. Joseph Mercy Hospital

Ann Arbor, Michigan, 48106, United States

RECRUITING

Henry Ford Hospital

Detroit, Michigan, 48202, United States

RECRUITING

Genesys Hurley Cancer Institute

Flint, Michigan, 48503, United States

RECRUITING

Herbert Herman Cancer Center, Sparrow Hospital

Lansing, Michigan, 48912, United States

RECRUITING

Ascension St. Mary's

Saginaw, Michigan, 48601, United States

RECRUITING

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

RECRUITING

University of Rochester - Wilmot Cancer Institute

Rochester, New York, 14642, United States

RECRUITING

Strecker Cancer Center-Belpre

Belpre, Ohio, 45714, United States

RECRUITING

Aultman Hospital

Canton, Ohio, 44710, United States

RECRUITING

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

RECRUITING

Arthur G. James Cancer Hospital & Richard Solove Research Institute

Columbus, Ohio, 43210, United States

RECRUITING

Columbus Oncology & Hematology Associates Inc

Columbus, Ohio, 43214, United States

RECRUITING

The Mark H. Zangmeister Center

Columbus, Ohio, 43219, United States

RECRUITING

Doctors Hospital

Columbus, Ohio, 43228, United States

RECRUITING

Adena Regional Medical Center

Columbus, Ohio, 45601, United States

RECRUITING

Dayton Clinical Oncology Program

Dayton, Ohio, 45420, United States

RECRUITING

Dayton Physicians LLC

Dayton, Ohio, 45420, United States

RECRUITING

Delaware Health Center

Delaware, Ohio, 43015, United States

RECRUITING

Marietta Memorial Hospital Cancer Center

Marietta, Ohio, 45750, United States

RECRUITING

Marion General Hospital

Marion, Ohio, 43303, United States

RECRUITING

Knox Community Hospital

Mount Vernon, Ohio, 43050, United States

RECRUITING

Licking Memorial Hospital

Newark, Ohio, 43055, United States

RECRUITING

Southern Ohio Medical Center

Portsmouth, Ohio, 45662, United States

RECRUITING

Genesis Health Care

Zanesville, Ohio, 43701, United States

RECRUITING

Wellspan Health - York Cancer Center

York, Pennsylvania, 17403, United States

RECRUITING

Harris Health Systems-Smith Clinic

Houston, Texas, 77030, United States

RECRUITING

Lester and Sue Smith Breast Center

Houston, Texas, 77030, United States

RECRUITING

Centra Lynchburg Hematology Oncology

Lynchburg, Virginia, 24501, United States

RECRUITING

Bon Secours Richmond Community Hospital Medical Oncology Assoc.

Mechanicsville, Virginia, 23116, United States

RECRUITING

Bon Secours St. Francis Medical Center

Midlothian, Virginia, 23114, United States

RECRUITING

Bon Secours Richmond Community Hospital at St. Mary's

Richmond, Virginia, 23226, United States

RECRUITING

West Virginia University

Morgantown, West Virginia, 26506, United States

RECRUITING

Ascension St. Elizabeth Hospital

Appleton, Wisconsin, 54915, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; Cyclophosphamide; Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Norman Wolmark, MD

  NSABP Foundation Inc

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Director, Department of Site and Study Management

CONTACT

1-800-270-3165; industrytrials@nsabp.org

Study Design

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

Study Record Dates

• First Submitted: January 12, 2018
• First Posted: January 26, 2018
• Study Start: May 14, 2018
• Primary Completion: October 30, 2023
• Study Completion: October 30, 2023
• Last Updated: March 6, 2023

Record last verified: 2023-03

Locations

US (43)