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HER2-negative Breast CancerPhase 2FB-12NCT03412643

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

A Phase 2 study testing Doxorubicin, Cyclophosphamide and Weekly Paclitaxel in people with HER2-negative Breast Cancer, run by NSABP Foundation Inc at 43 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
HER2-negative Breast Cancer
What is being tested?
Doxorubicin, Cyclophosphamide and Weekly Paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
64 participants
Where
43 sitesUnited States
Study dates
14 May 2018to 30 Oct 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.)
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  • 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.
  • 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.

Trial locations and contacts

43 sites in 1 country.

Director, Department of Site and Study Management contact

1-800-270-3165

industrytrials@nsabp.org

43 sites in 1 country

United States43 sites, 43 recruiting

  • St. Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106

    Recruiting

  • Ascension St. Elizabeth Hospital

    Appleton, Wisconsin, 54915

    Recruiting

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

    Recruiting

  • Strecker Cancer Center-Belpre

    Belpre, Ohio, 45714

    Recruiting

  • Aultman Hospital

    Canton, Ohio, 44710

    Recruiting

  • Cleveland Clinic Taussig Cancer Center

    Cleveland, Ohio, 44195

    Contact Person, 800-862-7798

    Recruiting

  • Arrowhead Regional Medical Center

    Colton, California, 92324

    Recruiting

  • Arthur G. James Cancer Hospital & Richard Solove Research Institute

    Columbus, Ohio, 43210

    Recruiting

  • Columbus Oncology & Hematology Associates Inc

    Columbus, Ohio, 43214

    Recruiting

  • The Mark H. Zangmeister Center

    Columbus, Ohio, 43219

    Recruiting

  • Doctors Hospital

    Columbus, Ohio, 43228

    Recruiting

  • Adena Regional Medical Center

    Columbus, Ohio, 45601

    Recruiting

  • Dayton Clinical Oncology Program

    Dayton, Ohio, 45420

    Recruiting

  • Dayton Physicians LLC

    Dayton, Ohio, 45420

    Recruiting

  • Cancer Care Specialists of Central Illinois

    Decatur, Illinois, 62526

    Recruiting

  • Delaware Health Center

    Delaware, Ohio, 43015

    Recruiting

  • Henry Ford Hospital

    Detroit, Michigan, 48202

    Recruiting

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

    Recruiting

  • Fort Wayne Medical Oncology and Hematology, Inc.

    Fort Wayne, Indiana, 46804

    Recruiting

  • Harris Health Systems-Smith Clinic

    Houston, Texas, 77030

    Recruiting

  • Lester and Sue Smith Breast Center

    Houston, Texas, 77030

    Recruiting

  • University of Iowa

    Iowa City, Iowa, 52242

    Recruiting

  • Herbert Herman Cancer Center, Sparrow Hospital

    Lansing, Michigan, 48912

    Recruiting

  • University of Louisville JG Brown Cancer Center

    Louisville, Kentucky, 40202

    Recruiting

  • Centra Lynchburg Hematology Oncology

    Lynchburg, Virginia, 24501

    Recruiting

  • Marietta Memorial Hospital Cancer Center

    Marietta, Ohio, 45750

    Recruiting

  • Marion General Hospital

    Marion, Ohio, 43303

    Recruiting

  • Bon Secours Richmond Community Hospital Medical Oncology Assoc.

    Mechanicsville, Virginia, 23116

    Recruiting

  • Mount Sinai Comprehensive Cancer Center

    Miami Beach, Florida, 33140

    Recruiting

  • Bon Secours St. Francis Medical Center

    Midlothian, Virginia, 23114

    Recruiting

  • West Virginia University

    Morgantown, West Virginia, 26506

    Recruiting

  • Knox Community Hospital

    Mount Vernon, Ohio, 43050

    Recruiting

  • Edward Hospital Cancer Center

    Naperville, Illinois, 60540-7499

    Contact Person, 630-527-7336

    Recruiting

  • University Medical Center New Orleans

    New Orleans, Louisiana, 70112

    Recruiting

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

    Recruiting

  • Licking Memorial Hospital

    Newark, Ohio, 43055

    Recruiting

  • University of Florida Cancer Center at Orlando Health

    Orlando, Florida, 32806

    Recruiting

  • Southern Ohio Medical Center

    Portsmouth, Ohio, 45662

    Recruiting

  • Bon Secours Richmond Community Hospital at St. Mary's

    Richmond, Virginia, 23226

    Recruiting

  • University of Rochester - Wilmot Cancer Institute

    Rochester, New York, 14642

    Recruiting

  • Ascension St. Mary's

    Saginaw, Michigan, 48601

    Recruiting

  • Wellspan Health - York Cancer Center

    York, Pennsylvania, 17403

    Contact Person, 717-741-8100

    Recruiting

  • Genesis Health Care

    Zanesville, Ohio, 43701

    Recruiting

Other trials in United States

About this study

Official title: An Open-Label Phase II Trial to Evaluate the Efficacy and Safety of Neoadjuvant Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel Plus Trastuzumab and Pertuzumab in Early Stage HER2-Negative Breast Cancer Patients Selected With a Test Measuring Live Cell HER2 Signaling Transduction (FACT 1)

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.

Read the detailed 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.

Being tested
Doxorubicin, Cyclophosphamide, Weekly Paclitaxel, Trastuzumab, Pertuzumab
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
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DoxorubicinDrug

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

  • CyclophosphamideDrug

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

  • Weekly PaclitaxelDrug

    80 mg/m2 IV weekly for 12 doses

  • TrastuzumabDrug

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

  • PertuzumabDrug

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

  • Celcuity CELx HSFDiagnostic test

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

Study groups in NCT03412643
Study groupRoleWhat they receive
Arm 1ExperimentalCelcuity 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
Receives: Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Weekly Paclitaxel; Drug: Trastuzumab; Drug: Pertuzumab; Diagnostic Test: Celcuity CELx HSF

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 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)

  1. Pathologic complete response to study therapy (breast)

    Percentage of patients with absence of residual invasive cancer in H\&E slides of resected breast specimens following the completion of neoadjuvant systemic therapy

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

  2. Clinical complete response (both breast and axilla)

    Percentage of patients with clinical complete response (cCR) measured by physical examination of the breast and axilla

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

  3. Residual cancer burden (RCB)

    Combined index of pathologic measurements of residual tumor size and cellularity and number and size of regional lymph nodes

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

  4. Logistic regression

    Regression of quantitative CELx scores by pCR outcome

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

  5. Frequency of adverse events assessed by CTCAE 4.0

    Frequency of adverse events categorized using the NCI Common Terminology Criteria for Adverse Events version 4.0

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jan 2018
  2. Study start14 May 2018
  3. Primary completion30 Oct 2023 (estimated)
  4. Study completion30 Oct 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
64 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03412643
Sponsor's protocol ID
NSABP FB-12
Acronym
FB-12
Status last verified
Mar 2023
First submitted
12 Jan 2018
Last updated
6 Mar 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Doxorubicin, Cyclophosphamide and Weekly Paclitaxel in people with HER2-negative Breast Cancer, run by NSABP Foundation Inc at 43 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 6 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 43 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Director, Department of Site and Study Management (1-800-270-3165, industrytrials@nsabp.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathologic complete response (PCR) to study therapy (both breast and lymph node-combined; ypT0/Tis ypN0) (time frame: From initiation of study therapy to time of surgery, which is usually performed 3 to 4 weeks after completion of study therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03412643.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2023.

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